‘Broken Heart’ syndrome in Scotland: a case of Takotsubo cardiomyopathy in a recently widowed lady

Case report

A 76-year-old Caucasian female presented to the emergency department with a 4-hour history of central crushing chest pain, radiating to her left arm and jaw. This was associated with shortness of breath, nausea and sweating. There was no family history of cardiovascular disease. She was a smoker for over 50 years and denied any alcohol or illicit drug use. The patient revealed her husband had died just the previous week. She described her intense emotional struggle in coming to terms with the loss. Appropriate investigations were carried out, including an electrocardiogram (ECG), which revealed ST elevation in leads I, AVL, V2, V3 and V4 (Figure 1), findings indicative of an anterior STEMI. The cardiac enzyme Troponin T was elevated at admission (51 pg/mL) and after 12 h (to 759 pg/mL). The acute coronary syndrome (ACS) management protocol was followed according to local guidelines. Subsequent coronary angiography demonstrated a right dominant system with normal coronary vascular anatomy (Figure 2). A left ventricular (LV) angiogram revealed an ejection fraction of 30% with significant wall motion abnormalities: extensive antero-apical akinesis with apical ballooning and concentric hypertrophy of basal septal bulge (Figures 3(a) and (b)). These findings were consistent with a diagnosis of Takosubo cardiomyopathy (TCM). A transthoracic echocardiogram confirmed the LV abnormalities. The patient was commenced on Metoprolol and Ramipril. She was later discharged after making a full clinical recovery and investigations confirmed complete resolution. OPEN IN VIEWER

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Figure 2.

Coronary angiogram showing normal vasculature with no evidence of stenosis or obstruction.

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Figure 3.

LV angiograms in diastolic (a) and systolic (b) phase revealing extensive antero-apical akinesis with apical ballooning.

Discussion

The patient presented above represents one of the few cases of TCM reported in Scotland. TCM was first described by Dote and colleagues. ¹ They observed a case of LV apical ballooning that occurred in the absence of coronary artery disease. TCM was found to mimic the LV dysfunction seen after an MI, but lacked evidence of myocardial ischaemia. The term ‘Takotsubo’, derived from a Japanese word meaning ‘octopus pot’, relates to the distinctive ventricular morphology seen on echocardiography; namely, a wide ventricular base with a long thin neck and ballooned apex – akin to the shape of the pot used to catch octopuses. As the condition is often precipitated by an acutely distressing event, TCM is occasionally referred to as ‘heart break syndrome’ in the popular press.

The exact prevalence of TCM is unknown but estimates lie between 1% and 2% of those presenting with ACS or STEMI. ² There is a clear female preponderance (86–100% of cases), most of whom are post-menopausal. ³ Caucasian and Asian populations appear to be more affected compared to other ethnic groups. ⁴ The classical presentation involves anginal chest pain and dyspnoea following an acutely stressful event. ² Numerous triggers have been described including death of a loved one, non-cardiac illness, medical and surgical intervention, exercise and both illicit and prescription drugs. ² However, a large multicenter cohort found no clearly identifiable trigger in a third of cases. ⁵ The diagnosis therefore rests on ECG changes, cardiac enzyme levels and evidence of typical wall motion abnormalities. Bybee et al. ⁶ have proposed a set of diagnostic features (Table 1). These criteria acknowledge evidence that non-apical variants, such as mid-ventricular wall motion abnormalities, occur frequently in TCM. For example, Eitel et al. ⁵ found that 17% of patients (n = 40) presented with a midventricular variant with apical sparing.

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Table 1.

Mayo criteria for the diagnosis of Takotsubo cardiomyopathy (adapted from Bybee et al. ⁶ ).

Proposed Mayo criteria a

1. Electrocardiographic abnormalities (ST-segment elevation followed by T-wave inversion)

2. Transient apical and mid-ventricular wall motion abnormalities (akinesis or dyskinesis)

3. Absence of obstructive coronary artery disease or evidence of acute plaque rupture

4. Absence of the following:

a. Recent significant head trauma

b. Intracranial haemorrhage

c. Pheochromocytoma

d. Another aetiology of myocardial dysfunction

The recent emergence of cardiovascular magnetic resonance (CMR) now provides a non-invasive means of characterising pathophysiological features of myocardial injury.^7,8 CMR can therefore aid in the evaluation of suspected TCM through the accurate differentiation between features of reversible (e.g. myocardial oedema, inflammation) and irreversible myocardial injury (e.g. necrosis). ⁵ Further large multicenter studies are required to establish diagnostic criteria based on CMR findings.

The pathophysiology of TCM is not clearly understood. There may be an element of transient multi-vessel epicardial vasospasm, leading to a region of stunned myocardium. ⁹ Likewise, rupture of an atherosclerotic plaque, resulting in temporary occlusion of a variant left anterior descending artery, may represent a pathogenic mechanism. ¹⁰ However, these hypotheses fail to explain the discrepancy between severe ventricular dysfunction and only slight increases in cardiac enzymes, the lack of pre-existing coronary artery disease and the pattern of ventricle wall motion dysfunction. It has been suggested that abnormal myocardial micro-perfusion along specific LV segments might lead to the wall motion abnormalities typically observed in TCM. ¹¹ However, again, it is difficult to support this hypothesis with no evidence of myocardial ischaemia. In fact, lack of myocardial ischaemia and evidence of ventricular dysfunction extending beyond the territory of a single epicardial coronary artery are two features central to the enigma of this condition.

Despite the apparent cryptogenic nature of TCM, the frequency of reported cases displaying a stressful event prior to the onset of symptoms suggests a causal link. The temporal relationship between a stressful trigger and the onset of symptoms in TCM has been found to correspond to the rise in catecholamine levels. ¹² This rise in circulating catecholamines, detected after an emotional trigger has been implicated in myocyte injury via a rise in intracellular calcium and oxygen-free radicals. A similar picture of catecholamine-induced damage is seen in cases of cardiomyopathy secondary to phaeochromocytoma. Researchers have also observed regional differences in the β-adrenergic receptor density in the apex and in the base of the left ventricle, may account for the ballooning pattern observed in TCM. ¹³ These observations are likely to have therapeutic implications as the use of metoprolol and prazosin can block β-and α-receptors respectively, and may therefore prevent apical ballooning.

Despite the plausibility of the hypothesis and some promising results, there is evidence to challenge the catecholamines hypothesis. For example, ambiguity remains over the precise temporal relationship between circulating catecholamines and the onset of symptoms. A rise in these hormones may in fact represent a consequence of the disease process rather than a causative factor. Furthermore, one study observed that catecholamine levels were elevated but remained so several days after clinical and functional resolution. ¹⁴ Although curious, this does not, however, exclude the possibility that a sudden rise in catecholamines levels may represent a trigger. The same study also found that only 9–18% of TCM cases had objective clinical signs of a hypercatecholamine state. ¹⁴ This observation could mirror the fact that a preceding stress event does not occur in a significant percentage of cases. ⁵ In these cases the clinical and pathological features of TCM may be reached via entirely different pathogenic mechanisms. Despite the contradicting evidence and apparent heterogeneity, most authors agree that sympathetic activity is likely to contribute to the pathogenesis of most TCM cases. Further research will be needed to clarify the roles of catecholamines and sympathetic activity in the disease process.

A hereditary component to the disease has been suggested, although, other than an observed disease association within family members, there is as yet no genetic evidence to support this. ¹⁵ The apparent stress triggers may in fact relate to a common social context. Further research is needed to determine the genetic and/or social risk factors for TCM.

Conclusion

The case presented above is consistent with the typical presentation of TCM. The recent death of the patient’s husband is likely to represent a key stress event and possibly a trigger. Further research is needed to determine the nature of the association between TCM and stress events. As the presentation, ECG changes and cardiac enzyme levels all mimic ACS, initial management should follow the ACS protocol. However, doctors must be aware of the specific characteristics of TCM, as the use of fibrinolytic therapy in the context of TCM is inappropriate and could potentially harm the patient. TCM should be considered if a female patient presents with features of ACS and investigations reveal no evidence of coronary artery disease. If TCM is suspected, the patient should be questioned regarding potential recent stress events. The management of TCM is largely supportive and the prognosis is excellent. For this reason the main risk to the patient is, in fact, inappropriate intervention.

Although well reported in the medical literature, this case of TCM has provided the basis for a discussion of the current understanding surrounding this perplexing condition. Further studies are necessary to observe the reliability of the clinical diagnostic criteria and further integrate the diagnostic advantages of CMR imaging. In addition, it is hoped that continued research will further elucidate pathogenic mechanisms. Once greater understanding is gained, we must seek a unifying consensus on the short- and long-term management of this unique cardiovascular condition.