Better Take a Second Look: The Fameless Face of Subacute Takotsubo Syndrome.

We have recently published in the journal the case of a 66-year-old female affected by typical Takotsubo syndrome (TTS) with apical ballooning, who presented important novel apical wall thickening despite normalization of left ventricular ejection fraction at a follow-up cardiac magnetic resonance (CMR) 1 month after the acute event. In the absence of significant elevated edema-sensitive T2 values at CMR, this constellation was interpreted as apical hypertrophic cardiomyopathy, initially mimicked by TTS. However, a routine late follow-up echocardiography and CMR after 6 months showed complete resolution of apical wall thickening. "Pseudohypertrophy" caused by transient significant myocardial edema seems to be a more frequent phenotype in the subacute phase of TTS than is yet known, which may cause diagnostic confusion. Copyright:

INTRODUCTION

Since the first description of Takotsubo syndrome (TTS), many studies have been performed regarding the acute and late stadium of the disease. The acute stadium of TTS is characterized by systolic dysfunction, mostly of the apical segments of the left ventricle. While left ventricular systolic function rapidly recovers, diastolic dysfunction and myocardial edema may persist for months.

Nevertheless, little is known about the imaging characteristics of subacute stadium of TTS.

We here report the case of a patient with significant transient apical wall thickening, in the subacute phase of TTS, which led initially to misdiagnosis of apical hypertrophic cardiomyopathy.

CASE REPORT

We have recently published in the journal the case of a 66-year-old female presenting with typical TTS showing apical ballooning on transthoracic echocardiography (TTE).

A first TTE control 1 week after the acute event revealed progressive thickening of the apical wall segments, while apical ballooning was resolving. Furthermore, electrocardiogram (ECG) changed and, as expectable in TTS, showed the transformation of ST-segment elevation to negative T-waves in precordial and inferior leads [Figure 1]. The patient was doing well and was discharged on ace inhibitor and beta-blocker.

Figure 1

(a) Acute stadium: Apical ballooning. 1 month: significant apical wall thickening. 6 months: normalization. (b) Acute stadium, 1 month: diastolic dysfunction Grade I. 6 months: normalization. (c) Acute event: ST-segment elevation. 1 month: Negative T-waves. 6 months: normalization

3T cardiac magnetic resonance (CMR) was performed 1 month after the acute event. As negative T-waves persisted, we suspected an underlying apical hypertrophic cardiomyopathy. Indeed, CMR confirmed significant apical wall thickening despite normalization of left ventricular systolic function and did not show neither late gadolinium enhancement nor evident signal increase in edema-sensitive T2-weighted images [Figure 2]. Interestingly, T1 mapping showed slightly increased T1 values of the apical and mid-ventricular segments. The finding was, therefore, initially interpreted as apical hypertrophic cardiomyopathy, which had been mimicked by apical TTS.

Figure 2

Cardiac magnetic resonance. (a) Cine. (b) T2 mapping. 1 month: Significant apical wall thickening. No significant increase of T2 value in apical segments, but difference of medium T2 value of apical and medial segments (48 ms) versus basal segments (35 ms). 6 months: normalization

Nevertheless, during a scheduled follow-up 6 months after the acute event, we observed normalization of the ECG [Figure 1]. TTE showed normal left ventricular ejection fraction (LVEF), normal regional wall motion, and normalization of apical wall segment thickness. Furthermore, diastolic function had turned normal [Figure 1].

Another CMR was performed, which confirmed TTE findings, showing normal apical wall segment thickness. Moreover, we repeated edema-sensitive T2-weighted images and reevaluated signal intensity. Indeed, compared to the first CMR, T2 values were globally lower (mean value 40 ms) [Figure 2].

Although T2 values of the first CMR were not significantly increased, there was a difference of signal intensity between thickened apical and normal basal wall segments of the left ventricle (apical mean value 48 ms vs. basal 35 ms) [Figure 2].

Taken together, after the second follow-up, we completely had to revise our first interpretation.

The patient did not present an apical hypertrophic cardiomyopathy, which had been mimicked by TTS, but a grossly evident transient apical wall thickening, due to edema in the subacute phase of TTS, despite normalization of regional wall motion and LVEF, which showed complete and spontaneous resolution after 6 months.

DISCUSSION

Since the first description of five cases in a Japanese textbook,[1] TTS has been considered a rare transient systolic left ventricular dysfunction in women of postmenopausal age, preceded by a negative emotional event, but in the past years, paradigms have changed.

TTS defines today a quite important percentage of definite diagnosis in patients presenting with initial suspect of myocardial infarction (1%–3% in men, 5%–6% in women). In the past years, a long way has been accomplished in studying TTS. Important knowledge was gained, for example, regarding triggers preceding the syndrome, which might be not only emotional but also physical stressors. TTS appears in various forms of systolic dysfunction. Among those, the apical (81.7%) and mid-ventricular forms (14.6%) remain the most frequent, while basal (2.2%) or focal forms (1.5%) are rarely seen.[2] Moreover, TTS is not the harmless transient systolic dysfunction it was initially thought to be but might be complicated by several, also live-threatening conditions.[3]

While it was first thought that recovery from TTS is rapid and complete, it has been shown that, despite normalization of LVEF, impaired diastolic function[4] and cardiac deformation indices may persist for several months.[5] Consistently with these findings, Neil et al. documented in a CMR study that myocardial edema, which is a well-known characteristic in the acute phase of TTS, can last up to 3 months[6] after the acute event.

It was shown that patients with TTS compared to the normal population had higher T2 intensity values after months and furthermore showed increased native T1 mapping values, suggestive for microscopic fibrosis.[7] We, therefore, interpreted the findings of the first CMR of our patient “a posteriori” as residual myocardial edema and beginning microscopic fibrosis in the thickened wall segments.

However, most studies in TTS have been accomplished or in the acute phase or during late follow-up. There are only few data about characteristics of the subacute stadium of this disease.

Our case report as well as a few other previous case reports describes a phenotype of TTS, characterized by an apical “pseudohypertrophy” due to the development of significant myocardial edema in the former akinetic wall segments, despite normalization of LVEF in the subacute phase of TTS.

Izgi et al. report a similar case of evident myocardial edema 10 days after onset of TTS, with spontaneous resolution, as confirmed by TTE and CMR.[8] Furthermore, recently, Williams et al. described the case of a woman with recurrent TTS and transient apical wall thickening due to reversible myocardial edema.[9]

A retrospective study in 124 patients with typical apical TTS, characterized by apical ballooning, documented that 14% of the studied patients showed transient apical wall thickening. Interestingly, wall thickening appeared 14.6 ± 10.3 days after the acute event. In-hospital mortalities as well as cardiac complications were more frequent in patients with transient apical wall thickening.[10]

Taken together, these reports as well as ours support the hypothesis that normalization of LVEF does not mean to be equivalent to complete recovery from TTS. Instead, it seems that there might be “two stage” recovery in TTS, including a subacute stadium characterized by a phenotype of “pseudohypertrophy” with significant apical wall thickening due to myocardial edema, which might be more common than yet known.

Given the remarkable similarity to apical hypertrophic cardiomyopathy, this may cause important diagnostic confusion. Therefore, a follow-up study with TTE and/or CMR in the subacute phase seems to be of crucial importance.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.