International Journal of Cardiology 180 (2015) 255–257

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International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard

Letter to the Editor

Troponin I/ejection fraction ratio: A new index to differentiate Takotsubo cardiomyopathy from myocardial infarction Giuseppina Novo a,⁎, Salvatore Giambanco a, Vito Bonomo a, Maria Rita Sutera a, Francesco Giambanco b, Antonino Rotolo a, Salvatore Evola a, Pasquale Assennato a, Salvatore Novo a a b

Chair and Division of Cardiology, University of Palermo, Via del Vespro 129, 90127 Palermo, Italy Division of Cardiology, Ingrassia Hospital, Corso Calatafimi, Palermo, Italy

a r t i c l e

i n f o

Article history: Received 14 November 2014 Accepted 23 November 2014 Available online 26 November 2014 Keywords: Takotsubo cardiomyopathy Acute myocardial infarction Troponin Left ventricular ejection fraction

1. Introduction The clinical presentation of Takotsubo cardiomyopathy (TC) can often simulate an acute myocardial infarction (AMI), presenting with precordial pain or dyspnea, de novo electrocardiographic (ECG) modifications and raised cardiac biomarkers [1–3]. Pathogenesis and therapy of this disease are still controversial [4–7]. During the acute phase, when patients are admitted to coronary care unit, it is very important to discriminate between these two conditions, in order to provide the appropriate treatment strategy. As distinctive characteristic from myocardial infarction, troponin levels slightly increase in TC patients if compared with AMI, and this rise is disproportionate compared to left ventricular ejection fraction (LVEF) reduction [8]. Therefore, the diagnosis can be often reasonably suspected without performing coronary angiography, however this last is mandatory to exclude the more formidable diagnosis of coronary thrombosis. The aim of our study was to develop an index that can help to noninvasively distinguish between AMI and TC. On this basis, we evaluated the ratio between the peak troponin I and ejection fraction measured at admission (TEFR). ⁎ Corresponding author at: Chair and Division of Cardiology, University of Palermo, Via del Vespro 129, 90127 Palermo, Italy. E-mail address: [email protected] (G. Novo).

http://dx.doi.org/10.1016/j.ijcard.2014.11.186 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.

2. Materials and methods We enrolled consecutive patients admitted for TC and, as control group, AMI patients, both STEMI and NSTEMI. Patients were diagnosed with TC on the basis of the Mayo Clinic criteria [9]: – Transient hypokinesis, akinesis, or dyskinesis of the left ventricular mid-segments with or without apical involvement; the regional wall motion abnormalities extend beyond a single epicardial vascular distribution; a stressful trigger is often, but not always, present; – Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture; – New ECG abnormalities (either ST-segment elevation and/or T wave inversion) or modest elevation in cardiac troponin; and – Absence of pheochromocytoma or myocarditis.

Patients were included in the myocardial infarction group if they presented rise and/or fall of cardiac troponin with at least one value above the 99th percentile upper reference limit and at least one of the following criteria: symptoms of ischemia; new or presumed new significant ST-segment–T wave (ST–T) changes or new left bundle branch block (LBBB); development of pathological Q waves in the ECG; and imaging evidence of new loss of viable myocardium or new regional wall motion abnormality [10]. AMI patients were treated with primary PCI for STEMI patients or urgent/early invasive strategy for NSTEMI patients when appropriate [11,12]. AMI patients were enrolled if they were EF fraction-matched with TC patients (i.e.: EF in AMI equal or greater, or less than 5% of TC). Blood samples for the analysis of troponin were obtained at 4 to 8 h after the onset of symptoms and then every 24 h and during hospitalization. LVEF was measured during the echocardiographic evaluation, using the biplane Simpson's Method, from apical 2-chamber and 4-chamber views. The TEFR index was calculated by dividing the peak troponin I level by the LVEF measured during the acute phase. Continuous variables were expressed as mean ± SD, while categorical variables were expressed as percentages. Differences among groups were analyzed by using Student's t or using the (χ2) test as appropriate. A p b 0.05 was considered statistically significant. Receiver operating characteristic (ROC) curves of TEFR were performed to assess the value that with the best sensitivity and specificity could discriminate between TC and AMI patients.

3. Results In the present study, a total of 106 patients were analyzed: 53 of these were diagnosed as TC, while 53 were assigned to the control group of AMI. Table 1 describes the characteristics of the study population. According to literature most of TC cases were women, while there was a male predominance in acute coronary syndromes. The peak troponin I level was significantly lower in patients with TC than in the AMI group (6.52 ± 7.25 vs. 91.11 ± 117.91 ng/dl, p b 0.001). As stated in methods, patients were matched to controls for EF. The

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Table 1 Characteristics of the study population.

Age (mean ± SD) Women, n (%) LVEF (%) Family history, n (%) Smoking, n (%) Diabetes mellitus, n (%) Hypertension, n (%) Dyslipidemia, n (%) Obesity, n (%) Peak troponin I (ng/dl) TEFR

AMI (n = 53)

Takotsubo (n = 53)

p

64.98 ± 11.57 19 (35.85) 43.49 ± 8.71 23 (43.39) 24 (45.28) 22 (41.51) 36 (67.92) 35 (66.04) 15 (28.3) 91.11 ± 117.91 230.83 ± 323.74

66.11 ± 10.14 50 (94.34) 41.34 ± 7.66 21 (39.62) 14 (26.42) 10 (18.87) 40 (75.47) 27 (50.94) 11 (20.75) 6.52 ± 7.25 16.31 ± 19.58

0.593 b0.001 0.18 0.693 0.043 0.011 0.388 0.115 0.367 b0.001 b0.001

mean TEFR was 16.31 ± 19.58 in TC and 230.83 ± 323.74 in AMI patients (p b 0.001). The ROC curve analysis of TEFR was performed in order to evaluate the higher diagnostic accuracy of this parameter in differentiating TC cases from AMI patients, compared with peak troponin I level alone. A TEFR ≤60 was the cut-off value to differentiate TC from AMI, with a sensitivity of 96.23% and a specificity of 84.91% (p b 0.0001, Fig. 1).

evaluation of non-invasive parameters, such as cardiac biomarkers, is increasingly necessary in clinical practice. Recent studies have proposed some variables to noninvasively identify TC. It has been demonstrated that the analysis of specific findings (such as Q waves, ST-segment elevation and the QTc interval) of the standard 12-lead ECG on admission could help to distinguish TC from anterior AMI [18]. In 2014, Randhawa et al. have shown that the ratios of BNP/TnT and BNP/CKMB, obtained early during admission, are more accurate in differentiating TC from AMI than the value of BNP alone [19]. It is well known that troponin levels are higher in patients with ACS, compared with TC, LVEF being equal. Although troponin alone has been shown to be useful in the differential diagnosis, we have hypothesized that the TEFR index, derived from the ratio between peak troponin I level and LVEF, could be a more accurate, non-invasive parameter to identify this category of patients, especially during the acute phase, when an emergency treatment is required. When a TEFR value ≤60 is found, this may suggest the diagnosis of TC rather than AMI. The evaluation of this index could support the physician in the decision to avoid a potentially dangerous invasive strategy in old patients with several comorbidities and low thrombotic risk profile. Limitations of our study are the retrospective nature and the relatively small sample size, thus further studies are needed to confirm our result.

4. Discussion Stress cardiomyopathy or Takotsubo cardiomyopathy (TC) was recently described as a stress induced acute cardiac disorder, characterized by transient left ventricular dysfunction, mild increase in cardiac biomarkers and new ECG abnormalities that often simulates an acute coronary syndrome (ACS), with angiographically normal coronary arteries, in the absence of obstructive coronary artery disease [9,13]. Moreover, its common clinical presentation with chest pain and dyspnea, similar to that of AMI, requires an immediate differential diagnosis between the two conditions. The diagnosis of TC should be suspected when the severe LV dysfunction is out of proportion compared to the degree of elevation in cardiac enzymes, in opposition to AMI, where higher levels of troponin are usually found [14,15]. Patients with TC have been shown to have a complete recovery of LVEF and systolic function, which occurs within days or weeks after the onset of symptoms [16,17]. During the acute phase, coronary angiography remains the gold standard technique for the differential diagnosis; for this reason, the

TEFR 100 Sensitivity: 96,2 Specificity: 84,9 Criterion : ≤60

Sensitivity

80 60 40 20 0 0

20

40 60 100-Specificity

80

100

Fig. 1. ROC curve of TEFR. A TEFR value ≤60 is the cut-off to discriminate between TC and AMI with a sensitivity of 96.23% and a specificity of 84.91%; AUC 0.97 (95% confidence interval [CI] 0.914–0.993).

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ejection fraction ratio: a new index to differentiate Takotsubo cardiomyopathy from myocardial infarction.

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