Correspondence / American Journal of Emergency Medicine 33 (2015) 1515–1535
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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 airway 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 Supreme 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 devices, we may conclude that all 3 devices are equally effective during mechanical ventilation. Nevertheless, the efficiency of mechanical ventilation may be decreased with time when using the Cobra, thus increasing 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 application [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 http://dx.doi.org/10.1016/j.ajem.2015.06.040 References [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] Akça 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 cardiomyopathies, Takotsubo cardiomyopathy (TTC) represents an uncommon 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 syndrome 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.
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Correspondence / American Journal of Emergency Medicine 33 (2015) 1515–1535
Table 1 Sepsis and Takotsubo cardiomyopathy: case reports
Table 3 Takotsubo cardiomyopathy and sepsis: in-hospital vs. out-of-hospital mortality
Gender Age Isolated microrganism
Outcome
Author
Male Female Female Female Male Female Female Female Female Male
84 47 70 73 60 62 41 30 55 52
Kakroo et al, 2014 [10] Finsterer et al, 2014 [12] Nunez et al, 2014 [11] Galea et al, 2013 [13] Karvouniaris et al, 2012 [14] Odigie-Okon et al, 2011 [9] Lee et al, 2010 [7]
Female
65
Female
69
Pseudomonas pneumonia Streptococcus pneumoniae Klebsiella pneumoniae
Favorable Fatal Favorable Favorable Favorable Favorable Favorable Favorable Favorable Favorable
Female
40
Cytomegalovirus
Staphylococcus aureus Escherichia coli ESBL Babesia
Male Female Sepsis
Overall
Out-of-hospital
In-hospital
3719 833 (22.4%)
3300 702 (21.3%) 2598 (78.7%) 63 (1.9%)
419 131 (31.3%) 288 (68.7%) 42 (10.0%)
2886 (77.6%) 105 (2.8%)
P b.001
b.001
Multivariate analysis
Sarullo et al, 2009 [6] Palacio et al, 2009 [16]
Favorable Geng et al, 2008 [15] Favorable Ohigashi-Suzuki et al, 2007 [17] Favorable Greco et al, 2006 [8]
In-hospital TC Age (by 10-year increase) Male sex (reference: female) Sepsis
Odds ratio
95% CI
P
2.02 1.33 1.24 2.02
1.43-2.85 1.15-1.53 0.91-1.70 1.17-3.49
b.001 b.001 NS .011
(Japan, Diagnosis Procedure Combination database 2010-2013) [19].
Legenda: ESBL, extended spectrum β-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, stressinduced 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 sufficient cases of sepsis to give statistical comparisons, and odds ratio data. Of a total of 2340 articles found under the term Takotsubo cardiomyopathy, 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 favorable 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 performed 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)
P
2.44 (2.09-2.84)
b.05
2.04 (1.80-2.32) 10.48 (8.97-12.25)
b.001
5.12 (3.80-6.91)
b.001
Age N50 y 50-64 y N64 y
ref 1.01 (0.77-1.32) 1.04 (0.82-1.35)
NS NS
Gender Female Male
ref 2.07 (1.71-2.49)
b.001
Underlying critical illness (including sepsis) NO YES
ref 10.87 (9.08-13.08)
b.001
All
24701 (100%)
Sepsis (all)
Sepsis (fatal)
380 (21.6)
Female 21 994 (89.0%) Male 2707 (11.0%) Female 1426 (6.5%) Male 336 (12.4%) Female 296 (20.8%) Male 84 (24.9)
Multivariate analysis
(USA, National Inpatient Sample 2008 to 2009) [18].
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 apoptosis, and extracellular, e.g., alteration of the microcirculation, dysregulation of autonomic nervous system, release of inflammatory cytokines, and vasoactive substances such as nitric oxide, endothelin1, 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 infection (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 population (mean age, 81.7 ± 7.5 years), since it is known that female sex seems to be protective under sepsis conditions, where a complex network 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 deleterious 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 catecholamine plasma levels exert direct toxic effects on the heart [23,24]. The pathophysiologic mechanisms involved in catecholamineinduced cardiomyocyte toxicity may depend on inflammation, oxidative stress, and abnormal calcium handling resulting in myocardial 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 documented 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 multivariable 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) 1515–1535
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) http://dx.doi.org/10.1016/j.ajem.2015.06.030
References [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 cardiomyopathy): 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 cardiomyopathy: 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, Schirò M, et al. Tako-tsubo cardiomyopathy 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 syndrome: a potential role for cytomegalovirus infection. J Cardiovasc Med (Hagerstown) 2006;7:623–7. [9] Odigie-Okon E, Okon E, Dodson J, Vorobiof G. Stress-induced cardiomyopathy complicating severe babesiosis. Cardiol J 2011;18:83–6. [10] Kakroo MA, Chowdhury MA, Luni FK, Moza A, Bhat PK. Reverse Takotsubo cardiomyopathy: 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. Recurrent 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 cardiomyopathy. 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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[18] Brinjikji W, El-Sayed AM, Salka S. In-hospital mortality among patients with takotsubo cardiomyopathy: a study of the National Inpatient Sample 2008 to 2009. Am Heart J 2012;164:215–21. [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 Diagnosis 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. Sepsisinduced 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 infections in elderly patients. J Womens Health (Larchmt) 2015 [Epub ahead of print]. [22] Angele MK, Pratschke S, Hubbard WJ, Chaudry IH. Gender differences in sepsis: cardiovascular and immunological aspects. Virulence 2014;5:12–9. [23] Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Gerstenblith G, Wu KC, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005;352:539–48. [24] Nef HM, Mollmann H, Troidl C, Kostin S, Voss S, Hilpert P, et al. Abnormalities in intracellular Ca2+ regulation contribute to the pathomechanism of Tako-Tsubo cardiomyopathy. Eur Heart J 2009;30:2155–64. [25] Schmittinger CA, Wurzinger B, Deutinger M, Wohlmuth C, Knotzer H, Torgersen C, et al. How to protect the heart in septic shock: a hypothesis on the pathophysiology and treatment of septic heart failure. Med Hypotheses 2010;74:460–5.
Diagnostic value of lead aVR in acute coronary syndrome
To the Editor, The electrocardiogram (ECG) has a crucial role in the initial assessment and triage of patients with symptoms compatible with an acute coronary syndrome (ACS). Conventional ST-elevation myocardial infarction (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 negative poles of each of the 12 leads are considered. Maximal information could be garnered by either adding inverted leads or by simply considering 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 interventricular septum and the outflow tract of the right ventricle. This lead explores 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 standard 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 deviations (elevation or depression) could be secondary to anterior or inferior 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 information 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 lateral 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
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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 airway 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 Supreme 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 devices, we may conclude that all 3 devices are equally effective during mechanical ventilation. Nevertheless, the efficiency of mechanical ventilation may be decreased with time when using the Cobra, thus increasing 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 application [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 http://dx.doi.org/10.1016/j.ajem.2015.06.040 References [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] Akça 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 cardiomyopathies, Takotsubo cardiomyopathy (TTC) represents an uncommon 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 syndrome 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.
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Correspondence / American Journal of Emergency Medicine 33 (2015) 1515–1535
Table 1 Sepsis and Takotsubo cardiomyopathy: case reports
Table 3 Takotsubo cardiomyopathy and sepsis: in-hospital vs. out-of-hospital mortality
Gender Age Isolated microrganism
Outcome
Author
Male Female Female Female Male Female Female Female Female Male
84 47 70 73 60 62 41 30 55 52
Kakroo et al, 2014 [10] Finsterer et al, 2014 [12] Nunez et al, 2014 [11] Galea et al, 2013 [13] Karvouniaris et al, 2012 [14] Odigie-Okon et al, 2011 [9] Lee et al, 2010 [7]
Female
65
Female
69
Pseudomonas pneumonia Streptococcus pneumoniae Klebsiella pneumoniae
Favorable Fatal Favorable Favorable Favorable Favorable Favorable Favorable Favorable Favorable
Female
40
Cytomegalovirus
Staphylococcus aureus Escherichia coli ESBL Babesia
Male Female Sepsis
Overall
Out-of-hospital
In-hospital
3719 833 (22.4%)
3300 702 (21.3%) 2598 (78.7%) 63 (1.9%)
419 131 (31.3%) 288 (68.7%) 42 (10.0%)
2886 (77.6%) 105 (2.8%)
P b.001
b.001
Multivariate analysis
Sarullo et al, 2009 [6] Palacio et al, 2009 [16]
Favorable Geng et al, 2008 [15] Favorable Ohigashi-Suzuki et al, 2007 [17] Favorable Greco et al, 2006 [8]
In-hospital TC Age (by 10-year increase) Male sex (reference: female) Sepsis
Odds ratio
95% CI
P
2.02 1.33 1.24 2.02
1.43-2.85 1.15-1.53 0.91-1.70 1.17-3.49
b.001 b.001 NS .011
(Japan, Diagnosis Procedure Combination database 2010-2013) [19].
Legenda: ESBL, extended spectrum β-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, stressinduced 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 sufficient cases of sepsis to give statistical comparisons, and odds ratio data. Of a total of 2340 articles found under the term Takotsubo cardiomyopathy, 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 favorable 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 performed 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)
P
2.44 (2.09-2.84)
b.05
2.04 (1.80-2.32) 10.48 (8.97-12.25)
b.001
5.12 (3.80-6.91)
b.001
Age N50 y 50-64 y N64 y
ref 1.01 (0.77-1.32) 1.04 (0.82-1.35)
NS NS
Gender Female Male
ref 2.07 (1.71-2.49)
b.001
Underlying critical illness (including sepsis) NO YES
ref 10.87 (9.08-13.08)
b.001
All
24701 (100%)
Sepsis (all)
Sepsis (fatal)
380 (21.6)
Female 21 994 (89.0%) Male 2707 (11.0%) Female 1426 (6.5%) Male 336 (12.4%) Female 296 (20.8%) Male 84 (24.9)
Multivariate analysis
(USA, National Inpatient Sample 2008 to 2009) [18].
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 apoptosis, and extracellular, e.g., alteration of the microcirculation, dysregulation of autonomic nervous system, release of inflammatory cytokines, and vasoactive substances such as nitric oxide, endothelin1, 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 infection (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 population (mean age, 81.7 ± 7.5 years), since it is known that female sex seems to be protective under sepsis conditions, where a complex network 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 deleterious 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 catecholamine plasma levels exert direct toxic effects on the heart [23,24]. The pathophysiologic mechanisms involved in catecholamineinduced cardiomyocyte toxicity may depend on inflammation, oxidative stress, and abnormal calcium handling resulting in myocardial 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 documented 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 multivariable 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) 1515–1535
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) http://dx.doi.org/10.1016/j.ajem.2015.06.030
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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 assessment and triage of patients with symptoms compatible with an acute coronary syndrome (ACS). Conventional ST-elevation myocardial infarction (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 negative poles of each of the 12 leads are considered. Maximal information could be garnered by either adding inverted leads or by simply considering 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 interventricular septum and the outflow tract of the right ventricle. This lead explores 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 standard 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 deviations (elevation or depression) could be secondary to anterior or inferior 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 information 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 lateral 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
