Article

Post-partum hemorrhage complicated by reverse-Takotsubo cardiogenic shock; a novel therapeutic approach

a b s t r a c t

Takotsubo cardiomyopathy \(TTC\) is a type of transient, yet severe left ventricular systolic dysfunction, rarely complicating extreme Emotional stress (“primary” TTC) or critical medical/surgical illness (“secondary” TTC forms). Although usually reversible, TTC may result in cardiogenic shock with dismal prognosis. “Secondary” TTC forms are particularly in danger for this complication, bearing significantly worse short and long-term prog- nosis. Herein, we report a rare case of a life-threatening “secondary” TTC in a patient with post-cesarean section severe hemorrhage, and we point out that early co-administration of esmolol and levosimendan might be an ef- fective and safe therapeutic approach in “reversing” TTC-induced cardiogenic shock, especially when invasive therapeutic strategies are practically unfeasible.

(C) 2016

1. Main Text

Takotsubo cardiomyopathy is a form of severe left ventricular (LV) systolic dysfunction, rarely complicating extreme emotional stress (“primary” TTC) or critical medical/surgical illness (“secondary” TTC forms) [1,2]. It is considered to be caused secondary to sympathetic ner- vous system over-discharge, possibly through a mechanism of catecholamine-mediated cardiac toxicity [1]. Reverse TTC is a rare TTC variant which is typically characterized by basal and midventricular LV akinesis and sparing of the apex [3].

Although usually reversible, TTC may result in devastating cardio- genic shock with dismal prognosis [1]. In the setting of severe Medical emergencies (“secondary” TTC forms) [2], however, shock management may be particularly challenging. interventional procedures such as cor- onary angiography (CAA) and intra-aortic balloon counter-pulsation (IABP) might be time-consuming and potentially dangerous, while the use of exogenous catecholamines for Circulatory support might further augment TTC. Herein, we wish to report the rare case of a patient with post-cesarean section severe hemorrhage complicated by reverse TTC- induced cardiogenic shock; this patient was successfully treated with an early combination of short-acting intravenous beta-blocker esmolol and calcium channel sensitizer levosimendan. To our knowledge, this

* Corresponding author at: Biopolis, 41110 Larissa, Greece.

E-mail addresses: [email protected] (J. Papanikolaou), [email protected] (D. Makris), [email protected] (V. Tsolaki), [email protected] (K. Spathoulas), [email protected] (E. Zakynthinos).

is novel information and might be useful in the setting of life- threatening “secondary” TTC.

A 39-year-old woman suffered massive blood-loss after a cesare- an section and was urgently re-operated for uterus Bleeding control. Upon ICU admission, despite hematocrit stabilization, the patient presented with severe hypotension, diaphoresis and oliguria. Nor- epinephrine requirements (<= 34 mcg/min) were continuously in- creasing, while lacticemia was gradually worsening (<= 5.7 mmol/L). Electrocardiogram did not reveal any pathological signs apart from sinus tachycardia (144 bpm). Echocardiography revealed typical fea- tures for reverse-TTC [2] and severely depressed cardiac output (2.7 L/min) (Fig. 1A-C; Supplementary Videos 1, 2). Elevated troponin-I values (1.5 ug/L) were disproportionately low to the extent of myo- cardial dysfunction; thus the diagnosis of reverse-TTC (instead of pregnancy-associated myocardial infarction) [4]-induced cardiogen- ic shock was established.

Invasive interventions (CAA, IABP) were primarily excluded due to ongoing bleeding diathesis and shock-induced renal dysfunction. Under the state of emergency, a pathophysiology-based two-step block- age of the catecholamine-mediated cardiac-stunning pathway was scheduled. Beta-blocker esmolol was used to protect the heart from cat- echolamine storm and counteract tachycardia; interestingly, esmolol dosage was aggressively up-titrated (0.04 mg/kg/min) to a targeted heart-rate <= 95 bpm, a practice which has been successfully utilized pre- viously in septic shock [5], yet analogous data is extremely sparse in TTC. In combination to beta-blockage, the non-catecholamine inotrope levosimendan [6] was utilized to restore myocardial contractility (0.05

http://dx.doi.org/10.1016/j.ajem.2016.12.034

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935.e2 J. Papanikolaou et al. / American Journal of Emergency Medicine 35 (2017) 935.e1935.e3

Fig. 1. Transthoracic echocardiography (parasternal long-axis views) upon admission revealing severely depressed left ventricular ejection fraction (approximately 20%), an “ace of spades”-systolic pattern (A,B) and moderate functional Mitral regurgitation (C), features typical for reverse Takotsubo Cardiomyopathy. All abnormalities totally restored on pre- discharge (ICU day-3) Echocardiographic examination (D,E,F). LV = left ventricle; LVEF = left ventricular ejection fraction; RV = right ventricle; MRJ = mitral regurgitant jet.

ug/kg/min, no-bolus), instead of exogenous catecholamine-inotropes (e.g. dobutamine), which might further precipitate the vicious-circle of stress-mediated myocardial damage [1].

Remarkably, central hemodynamics gradually improved, vasopres- sors were withdrawn and the patient was successfully extubated only 8 h later. There was no need for risky interventional procedures, neither bleeding relapse. Reverse-TTC echocardiographic pattern was partially inverted 18-h later (Supplementary Video 3), while cardiac function was totally restored upon discharge on ICU day-3 (Fig. 1D-F; Supple- mentary Video 4).

The rapid reversal of rTTC in our patient may ex-juvantibus highlight the relevance of TTC pathophysiology to strategies of clinical manage- ment. Certainly, case reports may be of less clinical value in advancing scientific knowledge and reviewing current therapeutic algorithms in rare diseases. However, our report may provide evidence that early co-administration of esmolol and levosimendan (possibly targeting at low heart-rates <= 95 bpm) might be an efficient and safe therapeutic al- ternative in TTC-induced shock, especially when invasive strategies are poorly-tolerated.

Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.ajem.2016.12.034.

Authors’ contributions

JP and EZ conceived of the study, participated in the interpretation of data, drafted and critically revised the manuscript for important

intellectual content. DM, VT and KS participated in the acquisition and interpretation of data and critically revised the manuscript for impor- tant intellectual content. All authors read and approved the final manuscript.

Patient’s informed consent

The patient provided written informed consent.

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Acknowledgments

There were no source(s) of support in the form of grants, gifts, equipment, and/or drugs.

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