Neurological and non-neurological triggers of Takotsubo syndrome in the pediatric population

Abstract

Takotsubo syndrome (TTS) is an acquired, transient type of systolicdysfunction, which mimics myocardial infarction clinically and electro-cardiographically [1]. TTS was first described in Japan in 1990 and oc-curs with an annual incidence of 30/1,000,000 [2]. TTS is also knownas stress cardiomyopathy, apical ballooning, broken heart syndrome,transient left ventricular/myocardial dysfunction, reversible acuteheart failure, neurogenic stunned myocardium, or acute catecholaminecardiomyopathy. By the American Heart Association (AHA) and theEuropean Heart Association (EHA) TTS is classified as unclassified car-diomyopathy [3]. TTS is usually diagnosed according to the revisedMayo Clinic criteria, but also Mayo clinic criteria [4], guidelines of theJapaneseCirculationSociety,JohnHopkinscriteria,Gothenburgcriteria,or Madias criteria may be applied [5]. There is post-menopausal femalepreponderance (90% of cases).Symptoms patients with TTS complain about depend on the locationof TTS and the type of complications ensuing and include anginal chestpain, dyspnea, leg edema, vertigo, fainting, fever, or neurological compli-cations. Abnormal biomarkers in TTS include elevated creatine-kinase(CK), elevated troponin, or elevated pro-brain-natriuretic-peptide(BNP). ProBNP may be particularly elevated in the acute phase of TTS[6]. CK, troponin, and proBNP values usually decline with resolution ofTTS[6].Theelectrocardiogram(ECG)showsabnormalitieslikeinmyocar-dialinfarction,withtypicaldynami csovertime.Echocardiographyshowsakinesia/hypokinesia/dyskinesia of the apical, mid-ventricular, or basalsegments of the left ventricular myocardium not confined to a vascularterritory. The classical type of TTS with typical apical ballooning onechocardiography is diagnosed if the apical or mid-apical segmentsare involved. The inverted type of TTS is diagnosed if the mid-, basal,or mid-basal ventricular segments are affected. In about one third ofthe adult cases the right ventricle is additionally involved promising apoor prognosis [7]. To meet the diagnostic criteria coronary arteriesneedtobenormalonangiography[4].ComplicationsofTTSmaybecar-diac or non-cardiac. Cardiac complications include heart failure, QT-prolongation, ventricular arrhythmias, intraventricular thrombusformation, cardiogenic shock, or sudden cardiac death. Non-cardiaccomplications include sepsis, pulmonary edema, anemia, ischemicstroke, peripheral embolism, or rhabdomyolysis.Therapyisusuallysupportiveandincludesapplicationofangiotensin-convertingenzymeinhibitors(ACEI),beta-blockers(BB),calciumantago-nists (CA), or diuretics. In case of sever e akinesia/hypokinesia/dyskinesiavitamin-K-antagonists should be applied to prevent from intra-cardiacthrombusformation.Acetyl-salicylicacidmaybehelpfultotreatconcom-itant coronary arterysclerosis. Inthe majority of the adult cases the prog-nosis is fair. Among 134 adult cases with TTS complete recovery wasobserved in 90% of the cases and a fatal outcome in 10% of the cases.Inverted TTS is regarded to have a worse prognosis than apical TTS atleast in adults [3]. Global akinesia/hypokinesia/dyskinesia has a poorprognosis. ECG in TTS normalizes within 10 weeks after onset and echo-cardiography within 6 weeks after onset [3].In the majority of the cases TTS is an abnormality of adulthood oc-curring between 60 and 75 y of age but TTS has been also reported inat least 28 pediatric patients so far (Table 1). The most frequent acutecentralnervoussystem(CNS)disorderstriggeringTTSinadultsaresub-arachnoidbleeding(SAB),epilepsy,andischemicstroke.MorerareCNSdisorderstriggeringTTSincludemigraine,posteriorreversibleencepha-lopathy syndrome (PRES), intra-cerebral bleeding (ICB), traumaticbrain injury (TBI), or infectious or immune encephalitis [3].Inareviewof 106 patients with SAB triggering TTS, age-at-event ranged between29–90 y but age-at-event was not available in 21 patients [3]. In a re-view of 9 patients experiencing TTS from intracerebral bleeding, age-at-event ranged between 23–94 y] [3 . When searching PubMed forthe terms “cerebral bleeding” or “subarachnoid bleeding” and “pediat-ric”, “child”,or“children” no hit could be obtained. In adults, intracere-bralbleedingisthe6thmostfrequentcauseofTTS[3].ThefrequencyofTTS triggered by acute CNS disorders in the pediatric population is un-known but as far as we know much lower than in adults. Only four