Recurrent Takotsubo cardiomyopathy in a postmenopausal Indian lady: Is there a pattern?

Takotsubo cardiomyopathy (TTC) is a syndrome of acute left ventricular dysfunction with a clinical presentation often mimicking acute coronary syndrome. Without a high index of suspicion, this clinical entity often goes unrecognized. Although initially categorized as a benign completely reversible condition, it is no longer considered to be so. Recurrence of this condition, though rare, has been reported in a non-Indian population. We present a case of recurrent TTC in a postmenopausal Indian lady who had a similar clinical presentation both at the index event and at recurrence.

Introduction

Takotsubo cardiomyopathy (TTC) is an increasingly recognized entity of acute clinical heart failure, with significant morbidity and an in-hospital mortality of 2–5%.[1] Although described more commonly in postmenopausal women of Caucasian and Asian ethnicity, no race may be exempt. Recurrence, although rare, often adds to the morbidity of the disease. However, a second episode has been reported occurring from 3 months to even 10 years after the index event. Here, we describe Takotsubo syndrome in a postmenopausal Indian lady, who 8 months after the index event, presented with a similar clinical presentation as at the first episode, despite being on optimal medical therapy.

Case Report

A 59-year-old postmenopausal Indian lady with no diabetes, hypertension, and prior cardiac or renal disease presented to the emergency room with episodes of giddiness and dyspnea of 4 hours duration. She reported no other symptoms. Couple of days prior to the presentation, she acknowledged a definite stressful event at home while preparing for her youngest daughter's marriage which was to be held in a few days. Clinical examination showed mild tachycardia and no features of overt heart failure.

Electrocardiogram at admission showed sinus tachycardia, J-point elevation and concave upward ST elevation in V2-V6, T wave inversion in aVL, and a QTc of 402 ms [Figure 1a]. Troponin T was elevated at 493 pg/mL (normal up to 14 pg/ml), and subsequent values showed a downward trend. NT Pro-BNP was 1348 pg/ml (normal up to 125 pg/ml). Screening for pheochromocytoma was negative (urinary metanephrines of 60 μg/24 h and normetanephrines of 311 μg/24 h). Chest radiography was noncontributory.

Figure 1

(a) Electrocardiogram on day 1. (b) Electrocardiogram on day 3

Echocardiography performed at admission showed moderate LV systolic dysfunction, regional wall motion abnormality involving the distal LV segments in a circumferential pattern-LV segments 13–17 (hypokinesia in apical inferior, apical lateral, apical anterior, apical septal areas and apex), but not corresponding to a single coronary arterial distribution [Figure 2], and preserved contractility of basal and mid LV segments. LV ejection fraction (EF) was measured as 37%, and there were no valvular abnormalities.

Figure 2

(a) Echocardiographic image in A4C view on day 1 showing wall motion abnormality. (b) Echocardiographic image in A4C view on day 4 showing complete recovery of wall motion abnormality

Her coronary angiography done 8 months ago was normal and hence not repeated. Considering a working diagnosis of TTC or myocarditis causing acute LV dysfunction, she was treated conservatively with beta-blockers, angiotensin converting enzyme inhibitors (ACEIs), and heparin.

Cardiac magnetic resonance imaging (CMRI) performed on day 2 showed preserved contractility of basal and mid LV segments, a kinetic apical segments, and apex of left ventricle with patchy edema and no myocardial late gadolinium enhancement. LV EF was 35% on CMRI. Classical MRI findings seen in myocarditis of mid myocardial late gadolinium enhancement was evidently absent. The absence of myocardial scar also ruled out myocardial infarction. Cardiac MRI favored a diagnosis of TTC [Figure 3].[2]

Figure 3

Two chamber end-diastolic (a), two chamber end-systolic (b) and four chamber end-systolic (c) steady state free precession images show apical ballooning with akinesis of the apical segments and apex of left ventricle (short arrows). (d) No enhancement (long arrows) seen on late gadolinium imaging

Electrocardiograms done on subsequent days showed deepening T wave inversions and prolonging QTc which peaked at a QTc of 642.25 ms by day 3 [Figure 1b]. On day 4, repeat echocardiography showed normal biventricular function with no wall motion abnormalities [Figure 2], further reiterating the diagnosis. By day 6, QTc interval normalized and T inversions decreased in amplitude, nevertheless, persisted. However, her in-hospital stay was free of significant arrhythmias. She was then discharged on ACEI and beta-blockers.

Eight months before, she was admitted with similar complaints of dyspnea and giddiness. Prior to that episode, she had to go through the tragic death of a close family member. On evaluation for the same, she was noted to have dynamic ECG changes similar to the present one and mild LV dysfunction with wall motion abnormalities involving the LV apical segments. She then underwent a coronary angiogram, which showed normal epicardial coronaries. She was initiated on regular medications and advised follow-up. Echocardiogram repeated 1 month later showed normal LV function with no wall motion abnormalities.

Discussion

Takotsubo is seen more commonly in postmenopausal women and is often precipitated by emotional or physical stress. However, a triggering event may not be identified in all. The incidence of this apical ballooning syndrome is 1.5–2.2%.[34]

Diagnosis is traditionally made using the modified Mayo Clinic criteria,[5] which require all the following criteria to be met: (a) transient wall motion abnormalities of LV which extend beyond a single epicardial vascular distribution; a stressful trigger is often seen but not always present; (b) absence of obstructive coronary disease or angiographic evidence of acute plaque rupture; (c) new electrocardiographic abnormalities (either ST-segment elevation and/or T wave inversion) or modest elevation in cardiac troponin; and (d) absence of pheochromocytoma or myocarditis. Our patient satisfied these criteria and also the European Heart Failure Association diagnostic criteria for TTC.[1]

Although prognosis is often considered good, especially if they survive the initial 48 h, it is no longer considered to be benign. In the initial 24–48 h of presentation, patients have a higher incidence of cardiogenic shock and cardiac arrhythmias, especially TdP (torsades de pointes) with grossly prolonged QTc, thus contributing to the mortality. The high catecholamine levels in TTC and the myocardial dysfunction mediated by it precludes the safe use of inotropes when they develop cardiogenic shock.

ECGs in TTC, although mimics acute coronary syndrome (ACS), demonstrate two distinct patterns – patients presenting with ST elevation ECG and those presenting with just T wave inversions. These ST elevations are often diffuse and concave upwards with no reciprocal changes. In this group of patients, T inversions appear when ST elevation subsides. In the second more common form, T inversions occurr from the beginning and persist without ST elevations.[6] Our patient had the former variety. The T inversion also has a specific pattern of evolution. Deepening T waves and progressively prolonged QTc intervals are often characteristic. Gradually, the QTc begins to normalize in 48–96 h.

Going by biomarkers, there often is a disproportionate rise in BNP/NT-proBNP compared to cardiac troponins. Contrary to ACS, the coronary arteries are typically open and the wall motion abnormality does not match that of any epicardial coronary artery territory.

Complete normalization of LV function and wall motion abnormalities generally takes approximately 4–8 weeks.[7] Sharkey et al. have demonstrated that in 5% of the cases normalization of LV EF can take 2.5–12 months.[8] However, in our case the ventricular function recovered by day 4.

Recurrence of TTC has been reported in literature at varying frequency, ranging from 2.7% to 11% over a 4-year period.[39] Singh et al.[10] reported a recurrence rate of 5% at 6 years (cumulative). Patients with severe TTC at index admission were noted to have higher recurrences. However, Parodi et al.[11] inferred that the severity of initial LV dysfunction does not impact long-term event rates. A retrospective analysis of 114 patients with recurrent TTC demonstrated that the pattern of clinical presentation is often similar to the index event,[12] but the pattern of LV involvement often may not be so. Brunetti et al.[13] and Singh et al.[10] documented that ACEI may be more effective than beta-blockers in preventing a recurrence of TTC. However, randomized controlled trials are lacking.

Our patient, even while on ACEIs since the first episode, had a recurrence of TTC with identical clinical pattern and similar echocardiographic form as at the first presentation. Although this may raise the possibility of genetic predisposition in developing a recurrence, there has been no conclusive evidence for the same.[14]

Conclusion

Recurrence of TTC, although rare, often follows similar clinical pattern of presentation as at the index event. Hence, with a high degree of suspicion and a careful history and clinical evaluation, the diagnosis can be established early. The predisposing factors and strategies to prevent a recurrence, however, need to be carefully studied.

Declaration of patient consent

The authors certify that appropriate patient consent was obtained.

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Conflicts of interest

There are no conflicts of interest.