Case report of a 66-year-old woman with atypical takotsubo syndrome and concomitant coronary artery disease

Abstract

Takotsubo syndrome is increasingly recognised worldwide. As both, takotsubo syndrome and acute myocardial infarction can present with similar findings, including chest pain, elevated troponin and creatine kinase, it is often difficult to differentiate these conditions. Here, we present a challenging case that illustrates (1) difficulties to diagnose takotsubo syndrome in the presence of a significant coronary artery stenosis; (2) how takotsubo syndrome could be misdiagnosed as acute coronary syndrome if diagnostic workup does not include echocardiography or left ventriculography; (3) the importance of cardiac MRI which can contribute to the diagnosis of takotsubo syndrome.

Background

Takotsubo syndrome, sometimes also referred to as ‘broken heart syndrome’ or ‘stress cardiomyopathy’, is an acute heart failure syndrome and an important differential diagnosis of acute coronary syndromes.¹ As takotsubo syndrome and acute coronary syndrome demonstrate many common features including symptoms, electrocardiographic changes and biomarker profiles, takotsubo syndrome could also be considered as a form of acute coronary syndrome.² While in acute coronary syndrome ischaemia is caused by a significant obstruction of a major coronary vessel due to plaque rupture, erosion or spasm, several mechanisms underlying takotsubo syndrome have been postulated. The most likely pathophysiologic concept is a severe and prolonged microvascular constriction. The first version of the Mayo Clinic Diagnostic Criteria in 2004 used significant coronary artery disease as an exclusion criterion for the diagnosis of takotsubo syndrome.³ In the revised and updated version of the Mayo Clinic Diagnostic Criteria in 2008, the authors pointed out that in rare cases a coronary artery stenosis might be concurrently present in takotsubo syndrome.⁴ There is still an ongoing debate about the relationship between coronary artery disease, with and without myocardial infarction, and takotsubo syndrome.⁵ Here we report a challenging case of takotsubo syndrome that illustrates the difficulties to diagnose takotsubo syndrome in the presence of significant coronary artery disease.

Case presentation

A 66-year-old woman was scheduled for a total left knee arthroplasty due to severe and symptomatic osteoarthritis. During the rapid sequence induction of general anaesthesia using remifentanil, suxamethonium and propofol and subsequent intubation, the patient’s blood pressure suddenly dropped. Despite use of norepinephrine, hypotension persisted and a pulseless electrical activity was recorded. Cardiopulmonary resuscitation was immediately started. After approximately 30 chest compressions and before the administration of epinephrine the return of spontaneous circulation was achieved. The orthopaedic surgery was postponed in order to investigate the causes of the cardiac arrest. The patient could be extubated within minutes. She had no chest pain or neurological deficit and was clinically stable.

Investigations

The review of the patient’s history revealed no previous cardiac events, and no other cardiovascular risk factors apart from smoking were present. There was a history of a panic disorder that was successfully treated with alprazolam. Immediately after return of spontaneous circulation, an ECG revealed sinus rhythm with no evidence of acute ischaemia (figure 1). High-sensitivity troponin T, myoglobin and creatine kinase, D-dimer and N-terminal-pro brain natriuetic peptide (NT-proBNP) were within normal limits (table 1). Within 1 hour, echocardiography revealed preserved left ventricular ejection fraction (biplane 55%) with akinesia in all midventricular segments and preserved function of all basal and apical segments (figure 2). These wall motion abnormalities clearly extended beyond a single coronary perfusion territory and a coronary angiography was scheduled. While waiting for coronary angiography, a repeat evaluation of cardiac biomarkers showed an increase in high-sensitivity troponin T (0.010–0.177 ng/mL, cut-off 0.014 ng/mL) and myoglobin (33–61 ng/mL, cut-off 58 ng/mL), whereas creatine kinase remained within the normal limits (table 1). Coronary angiography revealed one-vessel coronary artery disease: a medial subtotal occlusion of the left anterior descending artery that was treated with a drug-eluting stent (figure 3). No other lesions were documented (figure 3). Subsequent left ventriculography showed a midventricular takotsubo syndrome pattern that involved wall motion abnormalities not compatible with the territory of the subtotal coronary artery stenosis of the left anterior descending artery (figure 4). Wall motion abnormalities in left ventriculography were consistent with the echocardiographic findings, that is, circumferential akinesia of all midventricular segments and hyperkinesia of the apical and basal segments.

Figure 1.

The ECG revealed sinus rhythm without any evidence of acute ischaemia.

Table 1.

Time course of cardiac biomarkers

Cardiac biomarker (unit)	Cut-off	T0		+3 Hour		+24 Hour
High-sensitivity troponin T (ng/mL)	0.014	0.010	=	0.177	↑	0.029 ng/mL	↓
Myoglobin (ng/mL)	58	33	=	61	↑	41
Creatine kinase (U/l)	170	37	=	51	=	70	=
D-dimer (ng/mL)	660*	593	=
NT-proBNP (ng/L)	301*	58	=	331	↑	1338	↑

*Age-adjusted cut-off values.

NT-proBNP, N-terminal-pro brain natriuetic peptide.

Figure 2.

The echocardiography shows akinesia of all midventricular segments and hyperkinesia of all apical and basal segments (zoomed two-chamber and four-chamber views in systole and diastole).

Figure 3.

(A) Significant subtotal occlusion in the medial left anterior descending artery (zoomed in inset, right anterior oblique (RAO) 15°, cranial 22°). (B) Mid LAD (Left anterior descending artery) lesion after treatment with a drug-eluting stent (RAO 15°, cranial 22°). (C) Normal right coronary artery (left anterior oblique (LAO) 9°, cranial 22°).

Figure 4.

Ventriculography shows the midventricular takotsubo syndrome type (RAO 30°).

While high-sensitivity troponin T normalised within 24 hours, NT-proBNP increased significantly (table 1). Electrocardiography did not change throughout follow-up. A cardiac MRI scan 5 days later showed a substantial improvement as compared with the echocardiography findings with only mild circumferential mid wall hypokinesia mainly in mid anterior and mid inferior left ventricular wall segments with basal and apical segments’ hyperkinesia (figure 5A). Moreover, the T2-weighted short axis view (figure 5B) shows oedema especially in the mid anterior/anterolateral segments which further supports the diagnosis of takotsubo syndrome. No scars were seen in cardiac MRI (figure 5C). Videos (videos 1–11) illustrate the content of the figures.

Figure 5.

Cardiac MRI scan with (A) only mild circumferential mid wall hypokinesia mainly in mid anterior and mid inferior left ventricular wall segments with basal and apical segments’ hyperkinesia in end-systolic and end-diastolictwo-chamber cine view. (B) T2-weighted short axis view with oedema especially in the mid anterior/anterolateral segments. (C) Two-chamber late gadolinium enhancement shows no scars.

Video 1.

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DOI: 10.1136/bcr-2019-230164.video01

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Differential diagnosis

Several different diagnoses are possible explanations for these clinical findings. First, a non-ST-segment elevation myocardial infarction is unlikely due to the typical midventricular takotsubo pattern in the left ventriculography and echocardiography, the cardiac enzyme dynamics and the findings in cardiac MRI. In addition to that, pulseless electrical activity is very unlikely due to ischaemia. Also, the distribution of the wall motion abnormalities extends beyond the left anterior descending artery territory. There must be something else that could explain this finding. In non-ST-elevation myocardial infarction, cardiac troponin often shows a more pronounced and prolonged increase, whereas NT-proBNP is rarely that elevated. Second, a non-ST-segment elevation myocardial infarction with an unknown previous inferior wall motion abnormality and therefore outside the territory of the left anterior descending artery is also not possible. Because 5 days after the initial event in cardiac MRI no wall motion abnormalities were observed, which indicates transient wall motion abnormalities. Thirdly, an atypical midventricular takotsubo syndrome and simultaneously non-ST-segment elevation myocardial infarction is also unlikely. In a simultaneous presence of both conditions the cardiac biomarker dynamics would most likely have a more pronounced and longer course, and also in cardiac MRI oedema only in the territory of the stented lesion should be observed. Furthermore, in the context of non-ST-segment elevation myocardial infarction, late gadolinium enhancement and wall motion abnormalities can usually also be observed in the territory of the culprit lesion, this is not the case in our patient. The most likely diagnosis is atypical midventricular takotsubo syndrome with concomitant significant coronary artery disease in the absence of myocardial infarction. The stented lesion in the left anterior descending artery is most likely only an innocent bystander. The whole presentation of this patient can be explained by the atypical midventricular takotsubo syndrome alone. Anaesthesia induced stress and consequently a physical trigger for the takotsubo syndrome. On echocardiography, wall motion abnormalities with an atypical midventricular pattern were seen, on cardiac MRI 5 days later the transient nature of the wall motion abnormalities was documented. Additionally, cardiac enzyme dynamics also favours this diagnosis, as NT-pro-BNP is typically elevated in takotsubo syndrome, whereas cardiac troponins showed less pronounced dynamic than typically seen in myocardial infarction.

Treatment

The patient was discharged with aspirin 100 mg once daily, clopidogrel 75 mg once daily for 12 months, lisinopril 5 mg once daily and rosuvastatin 20 mg once daily. Aspirin and clopidogrel due to the drug-eluting stent, lisinopril due to observational data that supports angiotensin-converting-enzyme-inhibitors in takotsubo syndrome^{6 7} and rosuvastatin due to dyslipidaemia in the setting of significant coronary artery disease. No beta blocker was applied on discharge due to hypotension, however, 2 weeks later carvedilol 6.25 mg two times per day was initiated. Dual antiplatelet therapy could have been prescribed for only 6 months, as here a percutaneous coronary intervention in stable coronary artery was performed.⁸

Outcome and follow-up

After a follow-up period of 3 years the patient is free of cardiac symptoms with a very good functional capacity. The left ventricular ejection fraction appears normal. Several months later the total knee arthroplasty was successfully performed.

Discussion

This case highlights the diagnostic dilemma faced by cardiologists when takotsubo syndrome is present in a patient with a concurrent obstructive coronary artery disease. Indeed, in 2004 due to the limited knowledge about takotsubo syndrome criteria, this patient would have been diagnosed as non-ST-elevation myocardial infarction. In addition, this case outlines the significance of left ventriculography and echocardiography in the diagnosis of takotsubo syndrome. In 2018, we published an international consensus paper on the diagnosis and treatment of takotsubo syndrome,^{6 7} where we recognised the complex interaction of concomitant coronary artery disease in takotsubo syndrome. Interestingly, concomitant coronary artery disease is reported with a prevalence ranging from 10% to 29%. In this regard, patients with takotsubo syndrome and obstructive coronary artery disease are often misdiagnosed as classical acute coronary syndrome and differentiation can be challenging, as illustrated by this case report. Therefore, the presence of coronary artery disease should not be considered as an exclusion criterion for takotsubo syndrome, as recognised by present diagnostic criteria. In such patients, the wall motion abnormalities usually extend beyond the territory of the stenosed coronary artery. Furthermore, takotsubo syndrome may coexist with acute coronary syndrome and it has been reported that acute coronary syndrome itself may trigger takotsubo syndrome.^{6 7} In this patient, pulseless electrical activity was observed during anaesthesia. Anaesthesia and/or surgery is known to be a physical trigger for takotsubo syndrome.¹ We have recently reported that pulseless electrical activity is a possible life-threatening rhythm disorder in takotsubo syndrome.⁹ Pulseless electrical activity is possible at presentation, as in our patient, but also during the acute phase of the disease. The mechanisms for pulseless electrical activity are not fully understood, however, T-wave inversions and prolongation of the corrected QT interval were recorded more often in patients with takotsubo syndrome with cardiac arrest. This suggests that so far unknown electrical changes might be responsible for cardiac arrest and takotsubo syndrome. Usually, oedema is seen in takotsubo syndrome in cardiac MRI for months after the acute event and may thereby help to differentiate takotsubo syndrome from other possible diagnoses.^{6 7}

We have recently published an international expert consensus documents on clinical characteristics, diagnostic criteria and pathophysiology, diagnostic workup, outcome and management in takotsubo syndrome, and refer to these documents for a comprehensive overview on takotsubo syndrome.^{6 7}

This is an illustrative case that shows that takotsubo syndrome may very well be found in subjects with significant coronary artery disease. Furthermore, this case emphasises the importance of echocardiography or left ventriculography, if renal function or clinical situation allows and reminds clinicians that incomplete knowledge and diagnostic work up may lead to a false diagnosis and contribute to a wrong and underestimated incidence of takotsubo syndrome.

Learning points.

• Obstructive coronary artery disease no longer precludes the diagnosis of takotsubo syndrome.

• The evaluation of heart structure and function remains a critical assessment following a cardiac arrest.

• Echocardiography and left ventriculography play a crucial role in the differential diagnosis of takotsubo syndrome, allowing the assessment of the characteristic patterns of wall motion abnormalities.

• Takotsubo syndrome is a challenging diagnosis, and care must to taken in patients with obstructive coronary artery disease or unexplained biochemical elevations.

• Cardiac MRI is an additional diagnostic tool in takotsubo syndrome revealing myocardial oedema of the affected areas, usually in the absence of significant late gadolinium enhancement.