Abstract
Background
Takotsubo syndrome (TS) may be triggered by innumerable physical stress factors including epinephrine administration. The aim of this study is to report on the clinical features and outcome of epinephrine-induced TS (Epi-TS) in a large cohort of published cases.
Methods
A computer assisted search of the electronic data base Pubmed was performed from 1990 to 2014. All cases deemed to have Epi-TS were retrieved and compared to the large recent report by Templin et al. (All-TS).
Results
Thirty-three cases of Epi-TS were retrieved from the literature and compared to 1750 cases of All-TS. Chest pain as a presenting symptom occurred in 45% of cases. The Epi-TS patients were on average 20.6 years younger than All-TS patients (p < 0.0001). The women were still predominating in Epi-TS but in a significantly lower percentage compared to ALL-TS (73% in Epi-TS vs 89.8% in All-TS, p = 0.0054). One third of the Epi-TS cases had basal pattern of TS compared to 2.2% of cases reported in All-TS. Epi-TS cases were characterized by high complication rates, which occurred in 57.6%. The most important risk factor for the development of TS complication was the accidental administration (P < 0.001) and the dose of >1 mg epinephrine (p = 0.02). In spite of high complication rates, the recovery was rapid with no in-hospital mortality.
Conclusion
Epi-TS is characterized by a dramatic rapid onset of symptoms after epinephrine administration. Almost half of the cases had apical sparing and one third basal pattern of TS. In spite of high complication rates, the prognosis was good with no in-hospital mortality.
Highlights
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Published cases of Epinephrine-induced Takotsubo Syndrome (Epi-TS) are reviewed.
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Epi-TS is characterized by a dramatic clinical presentation and high complication rates.
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In spite of high complication rates, the prognosis of Epi-TS is good.
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Almost half of the cases of Epi-TS had apical sparing pattern of TS.
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The implications of the findings for the pathogenesis of TS are discussed.
1
Introduction
Takotsubo syndrome (TS) is an increasingly recognized acute cardiac disease entity. It has a clinical presentation resembling that of acute coronary syndrome (ACS) . The disease is characterized by a transient and unique pattern of circumferential left ventricular wall motion abnormality (LVWMA). It afflicts predominantly women and often preceded by an emotional or a physical stress factor . Countless physical stress factors including pheochromocytoma and epinephrine administration have been reported as a trigger factor for TS . Hitherto, epinephrine-induced TS (Epi-TS) has been described as case reports; only one report has been published on a series of 6 Epi-TS. The purpose of this study is to present the clinical features, TS localization pattern, the complication rates and the outcome of the Epi-TS in a relatively large cohort of 33 published cases . The implications of TS localization pattern for the pathogenesis of TS are also discussed.
2
Methods
All cases of epinephrine-induced TS or transient left ventricular dysfunction from 1990, the year where the Japanese term takotsubo was introduced, to December 2014 are critically reviewed. The cases were retrieved by searching in the pubmed using the search terms “takotsubo,” “apical ballooning,” “stress cardiomyopathy,” and “broken heart syndrome” and linking them with the terms “epinephrine,” “adrenaline,” and “catecholamines”. References were also checked for relevant articles including review papers. Only publications in English language (except one in French, where sufficient information could be obtained from the abstract in English and a table in the manuscript) were reviewed. In addition, adequate information could be acquired from only abstract in two further references with the use of only the available information in statistics. The following information was abstracted from the publications: the year of publications, age and gender of the patients, the indication, cause, route and the dose of epinephrine administration where available, the clinical presentation, the type of ECG changes and the cardiac biomarkers. The TS localization pattern was deemed by the description in the text or the available figures in the manuscripts. The hemodynamic complication rates after the presentation, the in-hospital mortality, the clinical course of the disease and the recovery/time where available were reviewed ( Table 1 ). Continuous variables are presented as means ± standard deviations and categorical data as absolute values and percentages. Fisher’s exact test or chi-square test was used as appropriate to compare categorical data, and 2-tailed unpaired student’s t test was used for continuous variables; a p < 0.05 was considered significant.
| Authors | Year | Age | Gender | Events for which Epin administered | Reasons for Epin administration | Presenting symptoms or manifestation | TS localization | Complications | Recovery/Time where available |
|---|---|---|---|---|---|---|---|---|---|
| Fyfe et al. | 1991 | 30 | Female | Cone biopsy of the cervix | Accidental | VES, VT | Global, Biventricular | Pulmonary edema and cardiogenic shock | Yes/10 days |
| Sato et al. | 2000 | 39 | Female | Surgery | Therapeutic | ES and increase in BP and HR | Global, biventricular | No | Yes/1 week |
| Budhwani et al. (abstract) | 2004 | 35 | Female | Cervix uteri injected | Accidental | Hemodynamic compromise | Severe LVD | Severe hemodynamic compromise | Yes |
| Kim et al. | 2008 | 47 | Male | Nasal operation | Therapeutic | Hypotension and tachycardia | Basal | No | Yes/2 days |
| Wong et al. | 2008 | 56 | Female | Hypotension | Therapeutic | Chest pain | Apical | No | Yes |
| Zubrinich et al. | 2008 | 76 | Female | Angioedema | Therapeutic | Chest pain | Apical | No | Yes/6 week |
| Lainez et al. | 2009 | 61 | Female | Suspected severe anaphylactic reaction | Therapeutic | LBBB in ECG | Apical | No | Yes |
| Abraham et al. | 2009 | 30 | Female | Suicide | Suicide | Chest pain | Apical | Heart failure | Yes |
| Abraham et al. | 2009 | 24 | Female | Liposuction | Inadvertent | Chest pain | Apical | Heartfailure | Yes |
| Abraham et al. | 2009 | 48 | Female | Face lift | Inadvertent | Chest pain | Basal | Heart failure | Yes |
| Abraham et al. | 2009 | 44 | Female | Keloid scar | Inadvertent | Chest pain | Basal | Heart failure | Yes |
| Abraham et al. | 2009 | 20 | Male | Colonoscopy | Inadvertent | Chest pain | Basal | Heart failure | Yes |
| Abraham et aal | 2009 | 54 | Female | Vasovagal syncope | Incorrectly | Chest pain | Basal | No | Yes |
| Manivannan et al. | 2009 | 41 | Female | Bee sting | Therapeutic, high dose | Chest pain | Mid-ventricular | No | Yes |
| Volz et al. | 2009 | 27 | Male | Self injection | Self injection | Circulatory failure | Mid-ventricular | Heart failure and cardiogenic shock | Yes/7 days |
| Litvinov et al. | 2009 | 24 | Female | Tomato anaphylaxis | Inadvertent | Chest pain | Basal | Heart failure and cardiogenic shock | Yes/7 days |
| Osuorji et al. | 2009 | 46 | Female | Status asthmaticus | Therapeutic | ECG changes | Apical | N/A | Yes/3 days |
| von Knobelsdorff-Brenkenhoff et al. | 2010 | 31 | Female | Endoscopic sinus surgery | Therapeutic | Non sustained VT | Mid-ventricular | No | Yes/7 days |
| von Knobelsdorff-Brenkenhoff et al. | 2010 | 59 | Male | Surgery | Therapeutic | SVES | Mid-ventricular | No | Yes/17 day |
| Morel et al. | 2010 | 16 | Male | Anaphylactic reaction | Therapeutic and then repeated accidental | Rapid hemodynamic deterioration | Basal | No | Yes |
| Härle et al | 2011 | 39 | Female | Diagnostic purposes | Accidental | Chest pain and dyspnea | Mid-ventricular | Pulmonary edema | Yes/10 days |
| Dewachter et al. | 2011 | 65 | Female | General anesthesia | Therapeutic | Hypotension and tachycardia | Apical | Pulmonary edema and shock | Yes/10 days |
| Magri et al. | 2011 | 26 | Female | Allergic reaction | Therapeutic | Chest pain or discomfort | Basal | No | Yes/2 weeks |
| Scheiba et al. | 2011 | 81 | Male | Hymenoptera sting | Therapeutic | Shock and unconsciousness | Apical | Unconsciousness, pulseless, cardiogenic shock, ventricular fibrillation which is defibrillated | Yes |
| Winogradow et al. | 2011 | 37 | Female | Bee sting | Therapeutic | Shortness of breath | Apical | Pulmonary edema and shock | Yes |
| Winogradow et al. | 2011 | 70 | Female | Wasp sting | Therapeutic | Chest pain | Apical | No | Yes |
| Patankar et al. | 2012 | 44 | Female | Angioedema | Incorrect dose | Hypotension and tachycardia | Apical | Shock and pulmonary edema | Yes |
| Kajander et al. | 2013 | 49 | Female | Anaphylactic reaction | Therapeutic | Chest pain | Basal | Heart failure, shock and unconsciousness | Yes/1 week |
| Copetti et al. | 2013 | 77 | Male | Cardiac arrest | Therapeutic | After resuscitation, the disease observed | Apical | cardiac arrest on admission, the disease recovered after 30 min) | Yes/30 min |
| Khoueiry et al. | 2013 | 44 | Female | Contrast allergy | Therapeutic | Chest pain | Basal | Pulmonary edema | Yes |
| Esnault et al. (French, abstract) | 2014 | 49 | Female | Operation | Inadvertent | N/A | Reverse (Basal) | Cardiogenic shock | Yes/4 days |
| Ituk et al. | 2014 | 54 | Male | Retrobulbar block | Therapeutic | Increase in BP and HR | Apical | Pulmonar edema and cardiogenic shock | Yes/1 day |
| Sundboll et al. (abstract) | 2014 | 67 | Male | Surgery | Therapeutic | Increase in BP and HR | Apical | N/A | Yes/5 days |
2
Methods
All cases of epinephrine-induced TS or transient left ventricular dysfunction from 1990, the year where the Japanese term takotsubo was introduced, to December 2014 are critically reviewed. The cases were retrieved by searching in the pubmed using the search terms “takotsubo,” “apical ballooning,” “stress cardiomyopathy,” and “broken heart syndrome” and linking them with the terms “epinephrine,” “adrenaline,” and “catecholamines”. References were also checked for relevant articles including review papers. Only publications in English language (except one in French, where sufficient information could be obtained from the abstract in English and a table in the manuscript) were reviewed. In addition, adequate information could be acquired from only abstract in two further references with the use of only the available information in statistics. The following information was abstracted from the publications: the year of publications, age and gender of the patients, the indication, cause, route and the dose of epinephrine administration where available, the clinical presentation, the type of ECG changes and the cardiac biomarkers. The TS localization pattern was deemed by the description in the text or the available figures in the manuscripts. The hemodynamic complication rates after the presentation, the in-hospital mortality, the clinical course of the disease and the recovery/time where available were reviewed ( Table 1 ). Continuous variables are presented as means ± standard deviations and categorical data as absolute values and percentages. Fisher’s exact test or chi-square test was used as appropriate to compare categorical data, and 2-tailed unpaired student’s t test was used for continuous variables; a p < 0.05 was considered significant.
