Letter to the Editor Acute renal failure, digoxin toxicity and brady-arrhythmia as possible triggers in Tako-Tsubo cardiomyopathy ☆ Francesco Santoro, Riccardo Ieva, Armando Ferraretti, Giuseppe Carpagnano, Michele Lodispoto, Luisa De Gennaro, Matteo Di Biase, Natale Daniele Brunetti ⁎ Cardiology Department, University of Foggia, Italy article info Article history: Received 8 October 2012 Accepted 1 November 2012 Available online 4 December 2012 Keywords: Tako-Tsubo cardiomyopathy Acute renal failure Digoxin toxicity Tako-Tsubo cardiomyopathy (TTC), also known as stress induced cardiomyopathy or apical ballooning syndrome, was first described by Dote in 1991 [1]. It is defined as a fully reversible acute deterioration of left-ventricular function, which is mainly found in women after an episode of emotional or physical stress (e.g. psychosocial stress, sepsis, surgery) [2]. The underlying mechanisms remain not completely known [3], although increased catecholamine levels were thought to be mainly responsible for TTC [4,5]. We report some cases in which acute renal failure and digoxin toxicity may have led to TTC. Case 1. An 83-year-old woman, hypertensive, diabetic, with chronic kidney disease, and chronic atrial fibrillation was referred for acute abdominal pain and diarrhea in the general surgery department. During the hospitalization, a week later, the woman presented reported dyspnea. Resting ECG showed low ventricular rate (40 bpm) atrial fibrillation, left anterior hemi-block, and negative T-waves in anterior leads (Fig. 1). Blood tests revealed increased digoxin levels (2.6 ng/ml, n.v. 0.9–2), acute renal failure (creatinine 3.46 mg/dl, n.v. 0.44–1), with cardiac troponin-I 1.58 ng/ml (n.v. 0–0.10). Echocardiography showed mild systolic dysfunction (left ventricular ejection fraction 48%) with apical dyskinesis and basal hyperkinesis, resembling apical balloon- ing typical of TTC. Coronary angiography showed mild coronary athero- sclerosis. The patient gradually recovered, and was discharged a week later, when all anomalies disappeared. Case 2. A 78-year-old woman with hypertension, diabetes, and chronic kidney disease, was referred for weariness and dyspnea [6]. Low ventricular rate (40 bpm) atrial fibrillation was present in the ECG, with right bundle branch block and left anterior hemi-block. Circulation digoxin levels were raised (2.8 ng/ml, n.v. 0.9–2), as well as creatinine levels (5.92 mg/dl, n.v. 0.44–1), with a diagnosis of acute renal failure. Digoxin, potassium and sodium levels recovered in a week, while creatinine levels remained increased (1.66 mg/dl) and troponin rose to 3.44 ng/ml (n.v. 0–0.10). Negative T-waves and apical dyskinesis and basal hyperkinesis characteristic of TTC appeared. Coronary angiography however was normal. The patient gradually recovered and was discharged in a week. In elderly patients chronic kidney disease is a common condition that represents a major public health problem and often coexists with cardiovascular disease and diabetes [7]. Moreover it is recog- nized as a risk factor for all-cause mortality and cardiovascular disease [8]. The combination of changes in the aging kidney, the abnormalities of other organ systems (congestive heart failure, hypertension, reno- vascular disease) and the exposure to various pharmaceutical agents (ACE-inhibitors, angiotensin receptor inhibitors and non-steroidal anti-inflammatory drugs) makes elderly individuals most susceptible for development of acute renal failure [9]. Elderly patients using digoxin for the management of high rate atrial fibrillation and heart failure may have episodes of acute renal failure that could have led to digoxin toxicity. As a matter of fact increased age (> 71 years) is most likely associated with enhanced susceptibility to digoxin toxicity, possibly due to pharmaco-kinetic changes [10]. We report two cases of a TTC probably triggered by increased catecholamine levels consequent to a brady-arrhythmia and digoxin toxicity. In both cases dehydration could have elicited acute renal failure that led to digoxin toxicity and brady-arrhythmias. Increased levels of digoxin seem to be related to higher concentrations of catecholamines. Plunkett et al. previously showed that a continuous digoxin infusion produces significant increases in the cerebro-spinal fluid norepinephrine [11]. Moreover bradycardias and complete atrio-ventricular block are well known to be characterized by an excess in internal adrenergic activation, presumably representing a finalized compensative mecha- nism [12,13]. We therefore hypothesize that acute renal failure a con- sequent digoxin toxicity and brady-arrhythmias could be related to increased levels of catecholamines responsible for the clinical onset of TTC. International Journal of Cardiology 165 (2013) e51–e52 ☆ 1) This paper is not under consideration elsewhere. 2) None of this paper's contents have been previously published. 3) All authors have read and approved the manuscript. 4) Authors have no potential conflict of interest to disclose. ⁎ Corresponding author at: Viale Pinto 1 71100 Foggia, Italy. Tel.: +39 3389112358; fax: +39 0881745424. E-mail address: nd.brunetti@unifg.it (N.D. Brunetti). 0167-5273/$ – see front matter © 2012 Elsevier Ireland Ltd. 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