Takotsubo cardiomyopathy, mental stress and the Kounis syndrome

Abstract

More than half a century ago, the renowned American physiolo-gist Walter B. Cannon [1] published a paper entitled VoodooDeath”, based on anecdotal experiences, largely from the anthropolo-gy literature, of death from fright. He postulated that such a deathwas caused “by a lasting and intense action of sympathico-adrenalsystem” [1,2]. Today's phrases “scared to death” [3] and “a brokenheart” [4] are deeply rooted in folk wisdom and reflect potentially le-thal consequences of emotional, depressogenic or mental stress. In1971, Engel [5] collected 170 accounts from the lay press of suddendeath that were attributed to disruptive life events. He found thatsuch events could be divided into 8 categories: (1) on the impactof the collapse or death of a close person; (2) during acute grief;(3) on threat of loss of a close person; (4) during mourning or onan anniversary; (5) on loss of status or self-esteem; (6) personalangeror threat of injury; (7)after danger is over;and (8) reunion,tri-umph, or happy ending. Engel proposed that any of these eventscould provoke neurovegetative responses, involving both the flight–fight and conservation–withdrawal systems, conducive to lethal car-diac events, particularly in individuals with preexisting cardiovascu-lar disease [5].Stress-induced cardiovascular reactivity has been shown to be as-sociated with carotid intima-media thickness and early atherogensis[6]. Daily stress is associated with a >2.1-fold increase in risk for de-veloping coronary artery disease and acute myocardial infarction [7],whichis similarto therelativerisksof diabetes,hypercholesterolemiaand hypertension [8]. Psychosocial stress accounts for 30% of the pop-ulation attributable risk of acute myocardial infarction [9]. Onlysmoking and hyperlipidemia account for greater population attribut-able risk, while hypertension, diabetes and abdominal obesity ac-count for lower population attributable risk [6,8,9].Takotsubo cardiomyopathy, alsoreferred to as transientleftventric-ular apical ballooning, stress-induced cardiomyopathy, takotsubo syn-drome, apical ballooning syndrome, atypical apical ballooning, ampullacardiomyopathy, broken heart syndrome, or transient left ventriculardysfunction syndrome [10], was named after a round-bottomed andnarrow-necked fishing pot – takotsubo 蛸壺 in Japanese – for trappingoctopus, because of its resemblance to the left ventriculogram in thesepatients.Itwas firstdescribedin1991byDoteetal. [11]andpopularized10 yearslaterbyTsuchihashietal. [12].Itisaclinicalconditionaffectingindividuals (mainly postmenopausal women), following emotional dis-tress,resemblingacutemyocardialinfarction,withusuallynormalcoro-nary arteries on coronary arteriography and transient left ventriculardysfunction. However, there are many questions regarding etiology,pathophysiology and treatment which still remain unanswered.In the very interesting article of Yoshida et al. [13] published inthis journal about a 78-year-old woman with takotsubo cardiomyop-athy, the patient developed cardiac rupture, massive hemorrhagicpericardial effusion and left ventricular mural thrombus. Fortunately,the patient survived after surgical performance of a pericardial win-dow and intravenous heparin therapy. Yoshida et al. [13] postulatedventricular rupture associated with coagulation abnormalities andcontraction band necrosis. Indeed, on light microscopy, increased eo-sinophilic staining with preservation of cross-striations and totaltransformation of the myocardial cytoplasm into dense eosinophilictransverse bands with intervening irregularity have been recognizedas the main findings of catecholamine-induced cardiomyopathysince long time ago [14]. Contraction-band necrosis has been de-scribed in clinical states of catecholamine excess such as pheochro-mocytoma [15] and subarachnoid hemorrhage [16]. It has also beenobserved post mortem in people who died under terrifying circum-stances such as fatal asthma [17] and violent assault [18], suggestingthat catecholamines may be an important link between emotionalstress and cardiac injury. In fact, takotsubo cardiomyopathy hasbeen reported following intravenous administration of epinephrineduring an anaphylactic reaction [19] and in association with pheo-chromocytoma [20].The precise incidence of patients with takotsubo cardiomyopathy isdifficult to ascertain, because its diagnosis has largely been a process ofexclusion [21]. The best estimate is 2.1% of female patients and 0.5% ofall patients with ST-elevation myocardial infarction, as reported in the