Takotsubo cardiomyopathy, sepsis and clinical outcome: does gender matter?

Correspondence / American Journal of Emergency Medicine 33 (2015) 15151535


Konstantinos Stroumpoulis, PhD

National and Kapodistrian University of Athens, Medical School MSc Cardiopulmonary Resuscitation,Athens, Greece

Androniki Palgimezi, PhD

General Hospital of Nikaia, Department of Anesthesiology

Athens, Greece

Fig. 2. Leak fraction at 25 minutes. Leak fraction = [ITV – ETV/ITV] * 100.

marginal statistical difference only with the Supreme supraglottic air- way device but seemed not to affect its clinical performance. Our study showed that the LV of the Cobra was greater than the LV of the Su- preme and i-gel. Probably, the cuff design of the Cobra does not offer as high a sealing pressure as that of the other devices. However, as a leak of 1 to 2 cm H2O does not affect the clinical performance of supraglottic de- vices, we may conclude that all 3 devices are equally effective during mechanical ventilation. Nevertheless, the efficiency of mechanical ven- tilation may be decreased with time when using the Cobra, thus increas- ing the risk for regurgitation and aspiration in these patients.

In our study, time for insertion was significantly lower for the i-gel than the other 2 devices. i-gel is made up of a thermoplastic elastomer with a noninflatable gel-like cuff that is claimed to achieve a rapid appli- cation [2]. Also, the longer time for correct insertion of the Cobra than Supreme may be explained partially by the fact that the first device has a larger inflatable cuff than the second airway device [3,4].

In conclusion, the difference in oropharyngeal leak pressure was not clinically important between groups. Each of the 3 devices appears to be effective in establishing an adequate airway during spontaneous and controlled mechanical ventilation.

Eleni Konstantogianni, MD Vassiliki Tsalkidou, MD Panagiota Dimou, PhD

General Hospital of Nikaia, Department of Anesthesiology, Athens, Greece

Athanasios Chalkias, PhD National and Kapodistrian University of Athens, Medical School MSc Cardiopulmonary Resuscitation,Athens, Greece

Hellenic Society of Cardiopulmonary Resuscitation

Athens, Greece Corresponding author. National and Kapodistrian University of Athens Medical School, MSc “Cardiopulmonary Resuscitation,” Hospital, “Henry Dunant,”

107 Mesogion Ave, 115 26, Athens, Greece Tel.: +30 210 4133992; fax: +30 210 6972396

E-mail address: [email protected]

Nicoletta Iacovidou, PhD

Hellenic Society of Cardiopulmonary Resuscitation

Athens, Greece National and Kapodistrian University of Athens, Medical School, 2nd Department of Obstetrics & Gynecology, Neonatal Division, Athens, Greece

Theodoros Xanthos, PhD National and Kapodistrian University of Athens, Medical School MSc Cardiopulmonary Resuscitation,Athens, Greece Hellenic Society of Cardiopulmonary Resuscitation, Athens, Greece


  1. Teoh WH, Lee KM, Suhitharan T, Yahaya Z, Teo MM, Sia AT. Comparison of the LMA Supreme vs the i-gel in paralysed patients undergoing gynaecological laparoscopic surgery with controlled ventilation. Anaesthesia 2010;65:1173-9.
  2. Francksen H, Renner J, Hanss R, Scholz J, Doerges V, Bein B. A comparison of the i-gel with the LMA-Unique in non-paralysed anaesthetised adult patients. Anaesthesia 2009;64:1118-24.
  3. Akca O, Wadhwa A, Sengupta P, Durrani J, Hanni K, Wenke M, et al. The New Perilaryngeal Airway (CobraPLA) is as efficient as the Laryngeal Mask Airway (LMA) but provides better airway sealing pressures. Anesth Analg 2004;99:272-8.
  4. Hooshangi H, Wong DT. Brief review: the Cobra Perilaryngeal Airway (CobraPLA and the Streamlined Liner of Pharyngeal Airway (SLIPA) Supraglottic airways. Can J Anaesth 2008;55:177-85.

Takotsubo cardiomyopathy, sepsis and clinical outcome: does gender matter??

To the Editor,

Infections and sepsis are important causes of cardiomyopathy, since they can affect ventricular function, systolic blood pressure, circulating volume and vessel tone, and so increasing mortality rate [1]. Among car- diomyopathies, Takotsubo cardiomyopathy represents an uncom- mon clinical condition characterized by a clinical picture similar to that of acute myocardial infarction [2] but with precise criteria for diagnosis [3]. It involves 1.7-2.2% of patients with suspected acute coronary syn- drome and is considered a typical gender-oriented disease, affecting mostly post-menopausal women following intense emotional or physical stress [4], including infections [5]. We sought to investigate across the available literature the possible difference by gender of mortality in TTC patients with sepsis.

Fig. 3. Time to successful airway device insertion. Time required for insertion was defined as

the time from the moment the airway device had come in touch with the upper incisors to the moment the first capnography tracing appeared [1,3].

? Financial Disclosure: This study is supported, in part, by a scientific grant (Fondo Ateneo Ricerca) by the University of Ferrara, Italy.

1526 Correspondence / American Journal of Emergency Medicine 33 (2015) 15151535

Table 1

Sepsis and Takotsubo cardiomyopathy: case reports



Isolated microrganism






Kakroo et al, 2014 [10]




Finsterer et al, 2014 [12]



Staphylococcus aureus


Nunez et al, 2014 [11]




Galea et al, 2013 [13]



Escherichia coli ESBL


Karvouniaris et al, 2012 [14]





Odigie-Okon et al, 2011 [9]




Lee et al, 2010 [7]







Sarullo et al, 2009 [6]





Palacio et al, 2009 [16]






Geng et al, 2008 [15]




Klebsiella pneumoniae


Ohigashi-Suzuki et al, 2007






Greco et al, 2006 [8]

Legenda: ESBL, extended spectrum ?-lactamase.

We systematically explored PubMed to identify case reports and case series reporting the possible association between sepsis and TTC. The keywords used were: Takotsubo (tako-tsubo) cardiomyopathy, stress- induced cardiomyopathy, Apical ballooning syndrome in combination with sepsis. For each case report, we collected gender, age, isolated microrganism, clinical outcome (favorable or fatal), author, and year of publication. For the case series, we were limited to studies with suffi- cient cases of sepsis to give statistical comparisons, and odds ratio data. Of a total of 2340 articles found under the term Takotsubo cardiomy- opathy, we extracted 38 papers reporting the association between TTC and sepsis. Among these, 12 were case reports (13 cases) [6-17], with an expected higher prevalence of women (n = 10/13, 76.9%) (Table 1). The mean age was 57.5 +- 13.6 years, and bacterial infections were more frequent (n = 11/13, 84.6%). In 7 cases (53.8%) there was the culture-based definition of the microrganism: bacterial (5/7, 71.4%), viral (1/7, 14.3%), and protozoan (1/7, 14.3%). Clinical outcome was favor- able in most cases (12/13, 92.3% of cases), and discharge occurred after a few days. As for case series, we identified two suitable studies, one per- formed in the United States [18] (Table 2) and one in Japan [19] (Table 3).

Table 2

Takotsubo cardiomyopathy and sepsis: in-hospital mortality

Mortality (OR, 95% CI)






21994 (89.0%)




Sepsis (all)

2707 (11.0%)

Female 1426 (6.5%)





336 (12.4%)


Sepsis (fatal)



10.48 (8.97-12.25)


296 (20.8%)


5.12 (3.80-6.91)


84 (24.9)

Multivariate analysis Age

N 50 y ref

50-64 y 1.01 (0.77-1.32) NS

N 64 y 1.04 (0.82-1.35) NS


Female ref

Male 2.07 (1.71-2.49) b.001

Underlying critical illness (including sepsis)

NO ref

YES 10.87 (9.08-13.08) b.001

(USA, National Inpatient Sample 2008 to 2009) [18].

Table 3

Takotsubo cardiomyopathy and sepsis: in-hospital vs. out-of-hospital mortality









833 (22.4%)


















Multivariate analysis




Odds ratio

95% CI


In-hospital TC




Age (by 10-year increase)




Male sex (reference: female)








(Japan, Diagnosis Procedure Combination database 2010-2013) [19].

Infections and sepsis are important causes of cardiomyopathy, and mechanisms may be both intracellular, e.g., alteration of the calcium transport, myofibrillar and Mitochondrial dysfunction, activation of ap- optosis, and extracellular, e.g., alteration of the microcirculation, dysreg- ulation of autonomic nervous system, release of inflammatory cytokines, and vasoactive substances such as nitric oxide, endothelin- 1, and catecholamines [20]. Sepsis seems to exhibit different outcome depending on sex. A recent study from our group [21] conducted in a large sample of elderly patients hospitalized for urinary trait infections showed that in-hospital mortality (IHM) was independently associated with sepsis (OR, 10.30; 95% CI, 6.11-17.46), Pseudomonas aeruginosa in- fection (OR, 2.54; 95% CI, 1.42-4.54), and female sex (OR, 2.32; 95% CI, 1.48-3.65). These results can be explained by the older age of the popu- lation (mean age, 81.7 +- 7.5 years), since it is known that female sex seems to be protective under sepsis conditions, where a complex net- work of cytokine, immune, and endothelial cell interactions occur and disturbances in the microcirculation cause organ dysfunction or even failure leading to high mortality. On the contrary, male sex may be del- eterious due to a diminished cell-mediated immune response. Male sex hormones, in fact, have been shown to be suppressive on cell-mediated immune responses. In contrast, female sex hormones exhibit protective effects which may contribute to the natural advantages of women under septic conditions [22].

Sepsis produces an overstimulation of the sympathetic nervous system, and considerable evidence indicates that high catechol- amine plasma levels exert direct toxic effects on the heart [23,24]. The Pathophysiologic mechanisms involved in catecholamine- induced cardiomyocyte toxicity may depend on inflammation, oxi- dative stress, and abnormal calcium handling resulting in myocardi- al stunning, apoptosis, and necrosis [25]. Although TTC is more prevalent in women and the great majority of the reported Clinical cases had a favorable outcome, a possible gender effect in clinical outcome, especially IHM in the presence of sepsis, seems to be doc- umented in the available studies. In the US study [18], accounting for 24 701 patients with TTC (89.0% women), IHM rate was 4.2%. However, male patients with TTC had a higher mortality rate than women (11.0% vs. 6.5%, OR 2.44), and those with sepsis as well (24.9% vs 20.8%; OR, 5.12). At the multivariate analysis, male sex had a mortality OR of 2.07. In the Japanese study [19], based on 3719 cases, patients with in-hospital TC had a higher proportion of men than out-of-hospital TC patients (31.3% vs 21.3%). In the multi- variable logistic regression analysis, in-hospital TC was significantly associated with higher (although not statistically significant) IHM in men (OR, 1.24), and in the presence of sepsis (OR, 2.02).

Alhough TTC mostly affects women, men are exposed to a worst clinical outcome and higher IHM in the presence of sepsis. Since their presentation to the ED, male patients suspected for TTC should be

Correspondence / American Journal of Emergency Medicine 33 (2015) 15151535 1527

carefully protected against infectious complications, since the onset of sepsis could be more harmful and life-threatening.

Fabio Fabbian, MD Alfredo De Giorgi, MD Ruana Tiseo, MD Benedetta Boari, MD

University of Ferrara, School of Medicine, Italy E-mail addresses: [email protected] (F. Fabbian) [email protected] (A. De Giorgi) [email protected] (R. Tiseo)

[email protected] (B. Boari)

Raffaella Salmi, MD

Ferrara General Hospital, Italy E-mail address: [email protected]

Fulvia Signani, PsyD

University of Ferrara, Italy E-mail address: [email protected]

Beatrice Zucchi, PedD Roberto Manfredini, MD?

University of Ferrara, School of Medicine, Italy

?Corresponding author at: Clinica Medica Unit, University of Ferrara School of Medicine, via Aldo Moro 8, 44124 Cona, Ferrara, Italy. Tel.: +39 0532 237166; fax: +39 0532 236816

E-mail addresses: [email protected] (B. Zucchi) [email protected] (R. Manfredini)


  1. Fernandes Jr CJ, Akamine N, Knobel E. Cardiac troponin: a new serum marker of myocardial injury in sepsis. Intensive Care Med 1999;25:1165-8.
  2. Kolkebeck TE, Cotant CL, Krasuski RA. Takotsubo cardiomyopathy: an unusual syndrome mimicking an ST-elevation myocardial infarction. Am J Emerg Med 2007;25:92-5.
  3. Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (Tako-Tsubo or stress car- diomyopathy): a mimic of acute myocardial infarction. Am Heart J 2008;155:408-17.
  4. Bossone E, Savarese G, Ferrara F, Citro R, Mosca S, Musella F, et al. Takotsubo cardio- myopathy: overview. Heart Fail Clin 2013;9:249-66.
  5. De Giorgi A, Fabbian F, Pala M, Parisi C, Misurati E, Molino C, et al. Takotsubo cardiomypathy and acute infectious diseases: a mini-review of case reports. Angiology 2015;66:257-61.
  6. Sarullo FM, Americo L, Accardo S, Cicero S, Schicchi R, Schiro M, et al. Tako-tsubo car- diomyopathy observed in a patient with sepsis and transient hypothyroidism. Monaldi Arch Chest Dis 2009;72:33-6.
  7. Lee S, Lee KJ, Yoon HS, Kamg KW, Lee YS, Lee JW. Atypical transient stress-induced cardiomyopathies with an Inverted takotsubo pattern in sepsis and in the postpartal state. Tex Heart Inst J 2010;37:88-91.
  8. Greco C, Saolini M, Mariani S, Santaniello E, Messa F, Tanzilli G, et al. Tako-tsubo syn- drome: a potential role for cytomegalovirus infection. J Cardiovasc Med (Hagers- town) 2006;7:623-7.
  9. Odigie-Okon E, Okon E, Dodson J, Vorobiof G. stress-induced cardiomyopathy com- plicating severe babesiosis. Cardiol J 2011;18:83-6.
  10. Kakroo MA, Chowdhury MA, Luni FK, Moza A, Bhat PK. Reverse Takotsubo cardiomy- opathy: a story of a critically ill man with transient cardiac dysfunction. Cardiology 2014;129:213-5.
  11. Nunez D, Bermejo R, Rodriguez-Velasco A. Takotsubo cardiomyopathy in the context of Staphylococcus aureus sepsis. Rev Esp Anestesiol Reanim 2014;61:150-3.
  12. Finsterer J, Stollberger C, Demirtas D, Gencik M, Ohnutek I, Hornykewycz A. Recur- rent Takotsubo syndrome in a patient with myotonic dystrophy 1. Acute Card Dis 2014;16(4):115-7.
  13. Galea F, Abela GP, Felice H. Takotsubo cardiomyopathy in chronic infection. Scott Med J 2013;58:e11-4.
  14. Karvouniaris M, Papanikolau J, Makris D, Zakynthinos E. Sepsis-associated takotsubo cardiomyopathy can be reversed by levosimendan. Am J Emerg Med 2012;30:832.e5-7.
  15. Geng S, Mullany D, Fraser JF. Takotsubo cardiomyopathy associated with sepsis due to Streptococcus pneumoniae pneumonia. Crit Care Resusc 2008;10:231-4.
  16. Palacio C, Nugent K, Alalawi R, Cevik C. Severe reversible myocardial depression in a patient with Pseudomonas aeruginosa sepsis suggesting tako-tsubo cardiomyopa- thy. Int J Cardiol 2009;135:e16-9.
  17. Ohigashi-Suzuki S, Saito Y, Tatsuno I. Takotsubo cardiomyopathy associated with sepsis in type 2 diabetes mellitus. Am J Emerg Med 2007;25:230-2.
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  19. Isogai T, Yasunaga H, Matsui H, Tanaka H, Ueda T, Horiguchi H, et al. Out-of-hospital versus in-hospital Takotsubo cardiomyopathy: analysis of 3719 patients in the Diag- nosis Procedure Nomination database in Japan. Int J Cardiol 2014;176:413-7.
  20. Romero-Bermejo FJ, Ruiz-Bailen M, Gil-Cebrian J, Huertos-Ranchal MJ. Sepsis- induced cardiomyopathy. Curr Cardiol Rev 2011;7:163-83.
  21. Fabbian F, De Giorgi A, Lopez-Soto P, Pala M, Tiseo R, Cultrera R, et al. Is female gender as harmful as bacteria? Analysis of hospital admissions for urinary tract in- fections in elderly patients. J Womens Health (Larchmt) 2015 [Epub ahead of print].
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Diagnostic value of Lead aVR in acute coronary syndrome

To the Editor,

The electrocardiogram (ECG) has a crucial role in the initial assess- ment and triage of patients with symptoms compatible with an acute coronary syndrome (ACS). Conventional ST-elevation myocardial in- farction (MI) criteria for diagnosing acute coronary occlusions have a low sensitivity (61%) and high specificity (96%) [1]. Currently, different methods are available such as placement of additional electrodes or even full-body surface maps [2]. Supplemental data are potentially available from the standard 12-lead ECG if both the positive and nega- tive poles of each of the 12 leads are considered. Maximal information could be garnered by either adding inverted leads or by simply consid- ering deviation of the ST segments in the opposite leads rather than only ST elevation in defined contagious lead [3-5]. In this brief report, we would like to emphasize the importance of new ST deviations of lead aVR and its reciprocal leads in patients with a clinical diagnosis of ACS. Lead aVR with multiple opposite leads has a paramount role in enhancing the emergency physicians’ ability for early diagnosis and to assist in determining the prognosis of patients with an Acute coronary occlusion.

Lead aVR can be used with the intent of obtaining information from the right superior side of the heart in the basal portion of the interven- tricular septum and the outflow tract of the right ventricle. This lead ex- plores ischemia of myocardial regions frequently missed by the other 11 leads of a conventional 12-lead ECG. In a 12-lead ECG, aVR does not have any contagious leads. There is a gap between leads I and II where the negative aVR (-aVR) fills this gap and assist in a comprehensive view of the frontal plane. Lead aVR is the only lead with 5 opposite leads a in 12-lead ECG. The unipolar lead aVR is reciprocal to the bipolar stan- dard limb leads I and II in the frontal plane and partly reciprocal to the unipolar chest leads of V5, V6, and V7 [2] (Figs. 1 and 2). The unique nonanterior and noninferior direction of lead aVR suggests that ST devi- ations (elevation or depression) could be secondary to anterior or infe- rior myocardial ischemia. The full spectrum of aVR ST changes should be viewed in conjunction to its opposite leads to localize the ischemic area and evaluate its prognostic significance. A shift in the ST segment of lead aVR can give specific information relating to ischemia of right upper portion of the heart, including the outflow tract of the right ventricle, the basal portion of the interventricular septum as well as reciprocal in- formation from inferior and lateral parts of the apical segment [6,7].

A transmural infarction of the basal interventricular septum produces an ST elevation in aVR and ST depressions in leads I and II and the left late- ral chest leads V5 to V7 (Fig. 3A and B). These leads are reciprocal to aVR, and their lead vector is opposite to the aVR vector. Likewise, a transmural