Possible Link Between Apical Ballooning Syndrome During Anaphylaxis and Inappropriate Administration of Epinephrine–1

Abstract

We read with interest the letter by Manivannan et al describing a patient with ABS due to intravenous epinephrine injection given for anaphylactic reaction after a bee sting. We would like to broaden the differential diagnosis in a scenario such as this. Acute coronary syndrome during an anaphylactic reaction, especially in those who receive epinephrine, can occur for a variety of reasons, including (1) ABS or stress cardiomyopathy, (2) allergic myocardial infarction (ie, Kounis syndrome [KS]), and (3) hypersensitive myocarditis (HM). Apical ballooning syndrome affects mainly women during emotional stress and is characterized by the presence of normal coronary arteries and reversible apical ventricular dysfunction. In this syndrome, it is thought that myocardial stunning occurs as a result of high levels of circulating (ie, endogenous) catecholamines. Epinephrine triggers a switch in intracellular signal trafficking in ventricular cardiomyocytes from Gs protein to Gi protein signaling via the β2-adrenoceptor, which in turn protects against the proapoptotic effects of the intense activation of β1-adrenoceptors. However, this change also causes a negative inotropic effect. Because β-adrenoceptor density is greatest at the apical myocardium, this effect is greatest in that region. Other mechanisms have also been implicated. It is not surprising that a supratherapeutic dose of intravenous epinephrine could produce a similar phenomenon, as postulated by Manivannan et al. However, this is not the first reported case of ABS due to the administration of epinephrine, as the authors claim. Six cases of stress cardiomyopathy due to epinephrine and 3 due to dobutamine were recently described by Abraham et al.1 The dose of epinephrine ranged from a minimum of 1 mg to 40 mg. Some recent reports have even linked this syndrome to anaphylactic reaction.2 However, other possible etiologies of ABS after a bee sting must also be entertained. The coincidental occurrence of chest pain, electrocardiographic changes, and elevated troponin levels during anaphylactic reaction to bee sting has previously been described as KS by various authors.3 During hypersensitive reactions, sudden release of histamine and other inflammatory mediators from mast cells, macrophages, and T lymphocytes has been postulated to lead to coronary vasospasm and hence to acute coronary syndrome. A myocardial biopsy will reveal a normal myocardium. However, KS may occur in association with ABS because various cytokines have been implicated in the causation of ABS. In this context, exogenous administration of epinephrine is not required for the development of ABS. A case report of KS with ABS has been published.4 Hypersensitive reactions may also involve the heart by causing HM. In patients with HM, the myocardial biopsy will reveal the presence of eosinophils, atypical lymphocytes, and giant cells. Clinically, it is difficult to differentiate HM from KS because both present with signs and symptoms of acute coronary syndrome and for both coronary angiography reveals normal coronary arteries. The patient described by Manivannan et al had ventricular dysfunction typical of ABS in the presence of an anaphylactic reaction. Hence, we propose that she had KS complicated by ABS due to epinephrine and release of cytokines from the allergic reaction to the bee sting. As such, exogenous epinephrine administration need not be credited as the sole origin of ABS in this patient.