Transient left ventricular dysfunction syndrome during anaphylactic shock Vasospasm, Kounis syndrome or epinephrine-induced stunned myocardium? O. Morel a, ⁎, L. Jesel a , N. Morel b , A. Nguyen c , A. Trinh a , P. Ohlmann a , A. Imperiale d a Pôle d'activité médico-chirurgicale des Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, France b Pôle des Urgences adultes, service de réanimation des Urgences, Hôpital Pellegrin, Place Amélie-Raba-Léon, 33076 Bordeaux Cedex, France c Pôle de Pédiatrie, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, France d Service de Biophysique et de Médecine nucléaire, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, France article info Article history: Received 30 September 2009 Accepted 17 October 2009 Available online 14 November 2009 Keywords: Takotsubo Apical ballooning syndrome Breaking heart syndrome Myocardial infarction Acute coronary syndrome Catecholamines Transient left ventricular dysfunction syndrome (TVLDS) has been rarely observed during anaphylactic shock and its pathophysiology remains still enigmatic [1,2]. Multivessel epicardial coronary spasm or coronary microvascular impairment was suggested as primary causative mechanism. Alternatively, impaired coronary blood flow caused by vulnerable plaque rupture has been proposed as a direct cause of Takotsubo cardiomyopathy (TTC). The Kounis syndrome is a combination of acute coronary syndrome and anaphylactic reaction [3]. In this situa- tion, the release of various inflammatory mediators including histamine could induce a coronary artery spasm or erosion/rupture of an athero- matous plaque contributing to TLVDS [4]. Challenging this paradigm, a direct catecholamine acute toxicity was recently proposed as a causative mechanism of the stunned myocardium observed in TLVDS [5]. We report a patient with severe left ventricular systolic dysfunc- tion during anaphylactic shock. Whilst ECG depicted a drastic ST segment elevation in the anterior leads, cardiac catheterism confirms the co-existence of severe decrease of systemic vascular resistance and normal coronary angiogram. A 16-year old child (height: 172 cm, weight: 60 kg) with history of penicillin allergy was referred to our Intensive Pediatric Care Unit for anaphylactic shock and severe angio-oedema following a hymenopter bite. Sub-cutaneous epinephrine (1 mg) was initially administrated before the patient's arrival to the hospital. Given the persistence of hemodynamic instability, a treatment by intravenous epinephrine (0.2 mg), methylprednisolone (120 mg) and dexchlorpheniramine (5 mg) was initiated by the Medical Mobile Intensive Care Unit. On admission, Glascow scale score was 10, hemodynamic remains unstable with a blood pressure of 105/50 mmHg and heart rate of 100 beats per minute. First ECG showed sinusal tachycardia without significant ST segment elevation, hence a treatment by epinephrine 0.05 γ/kg/min and fluid therapy (crystalloid 1500 cc) was started. Accidentally, a bolus of epinephrine was administrated, producing a rapid degradation of hemodynamic with a blood pressure of 85/ 46 mmHg, tachycardia and alteration of consciousness. ECG docu- mented a drastic ST elevation in the anterior leads and mirrors signs in the inferior leads (Fig. 1A and B). The patient underwent urgent coronarography, which showed normal vessels and no evidence of vasospasm (Fig. 1C and D). Left ventriculography revealed basal hypokinesia with left ventricular ejection fraction (LVEF) of about 35%. There was no intra ventricular gradient. At the same time, a right heart catheterism was realized using a Swan Ganz catheter. Cardiac output determined by thermodilution was slightly elevated (7.7 L.min -1 ), and systemic vascular resistance were diminished at 6.9 UI Wood (552 dynes.sec.cm –5 ). Treatment by epinephrine was stopped and replaced by norepinephrine enabling swift hemodynamic stabilization. On admission, laboratory tests showed a moderate elevation of serum troponin (0.25 μg/L, peak at 7.06 μg/L 18h later), whereas CK remains on the normal range. Complete blood count revealed a white blood count cell of 17,800/mm 3 . The haemostasis and fibrinolysis parameters were also altered (INR at 59%, FV diminished at 59%, elevation of D- dimers at 2490 μg/L). In order to assess both left ventricular (LV) perfusion and myocardial sympathetic activity, the patient underwent myocardial 201 Thallium ( 201 Tl) Gated Single Photon Emission Computed Tomography (G- SPECT) and 123 I-mIBG SPECT, 8 and 10 days after anaphylactic shock, respectively (Fig. 2A and B). Hypocontractile anterior mid and basal LV segments were characterized by normal perfusion but reduced uptake of 123 I-mIBG. Follow-up 123 I-mIBG SPECT was performed 3 and 7 months after the first investigation showing progressive improve- ment until normalization of LV sympathetic innervation (Fig. 2C). At one month follow-up, total recovery of LVEF was documented by TTE. In the present report, three main hypotheses were raised to explain the pathophysiology of the occurred transient left ventricular dysfunc- tion syndrome: (i) epinephrine-induced vasospasm, (ii) Kounis syn- drome and (iii) epinephrine-induced stunned myocardium. (i) Myocardial ischemia-reperfusion due to epicardial, microvascu- lar spasm or aborted myocardial infarction and related no-reflow phenomenon, was first proposed to be a potent inducer of TLVDS [1]. In the present report, whilst ECG depicts a dramatic ST segment elevation following accidental epinephrine bolus, coronary angiography was normal and systemic vascular resis- tances were diminished. The possibility of a severe transient epicardial vasospasm induced by epinephrine toxicity cannot be ruled out categorically, because intravenous epinephrine has a very short half life and could have caused it before the coronary angiogram was performed. However, ST elevation was still evidenced when the angiography was performed. Although we did not evaluate coronary resistance or myocardial perfusion after physical or pharmacological stress, the rest perfusion that was assessed at the sub-acute phase by myocardial 201 Tl G-SPECT was normal. In the past, several authors had reported a diminished coronary flow reserve or reduced coronary flow velocity at the onset of TTC. These findings were first challenged by Abe et al. showing almost normal coronary flow reserve in TTC [6]. Other authors have also reported severe reduction of myocardial fatty acid or glucose metabolism coexisting with normal or minimally reduced perfusion in the apex or mid- ⁎ Corresponding author. Pôle d'activité médico-chirurgicale des Hôpitaux Universi- taires de Strasbourg, Nouvel Hôpital Civil,1, place de l'Hôpital, 67091 Strasbourg Cedex, France. Tel.: +33 369550949; fax: +33 388127203. E-mail address: olivier.morel@chru-strasbourg.fr (O. Morel). 501 Letters to the Editor