Cardiovasc Toxicol. DOI 10.1007/s12012-017-9428-9. Predicting Cardiotoxic Effects of Carbon Monoxide Poisoning. Using Speckle Tracking Echocardiography.
Predicting Cardiotoxic Effects of Carbon Monoxide Poisoning Using Speckle Tracking Echocardiography Erhan Saraçoğlu, Ertan Vuruşkan, Salih Kılıç, Yusuf Çekici, Bahaeddin Onur, Yavuz Arslan, Ertuğrul Kılıç & Ömer Aykut Cardiovascular Toxicology ISSN 1530-7905 Cardiovasc Toxicol DOI 10.1007/s12012-017-9428-9
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Author's personal copy Cardiovasc Toxicol DOI 10.1007/s12012-017-9428-9
Predicting Cardiotoxic Effects of Carbon Monoxide Poisoning Using Speckle Tracking Echocardiography Erhan Saraçoğlu1 · Ertan Vuruşkan2 · Salih Kılıç1 · Yusuf Çekici1 · Bahaeddin Onur3 · Yavuz Arslan4 · Ertuğrul Kılıç5 · Ömer Aykut6
© Springer Science+Business Media, LLC 2017
Abstract Carbon monoxide (CO) poisoning could cause significant cardiac injury. This study aimed to evaluate patients with CO poisoning by using speckle tracking echocardiography (STE), a potentially more sensitive technique, to identify left systolic ventricular dysfunction for the first time in the literature. Seventy-two patients who were exposed to CO poisoning were studied. Blood collection and echocardiography were performed at admission and after patients’ discharge on days 10–15 (mean 12 days). Global longitudinal strain (GLS) and global circumferential strain (GCS) were calculated using STE. In order to find the normal strain levels and to compare it to the patient with CO poisoning, 35 healthy subjects were included in the study. Left ventricular ejection fraction was analyzed according to Simpson’s method. Patients were divided into two groups based on their LVEF values. LVEF 60 frames/s). Global and segmental LV LS and CS were calculated [9]. The LV CS was analyzed in basal, medial, and apical short-axis views, and the LV LS was analyzed in four-, two-, and three-chamber views. The endocardial border was manually traced at the end-diastole. Tracking was then performed, and the strain–time curves were obtained automatically. The strain–time curves were analyzed manually, and if tracking was suboptimal, the endocardial border was retraced. If satisfactory tracking was not accomplished within three attempts, nontracking segments were excluded from the analysis. Peak LS measurements were obtained
from 17 regional segments and peak CS measurements, from 12 regional segments. The regional strain values were averaged to determine the global longitudinal strain (GLS) and global circumferential strain (GCS). Statistical Analysis The continuous variables (numeric variables: age, GLS, LVEF, etc.) that were expressed as mean ± standard deviation and the categorical variables (a finite number of categories or distinct groups: diabetes mellitus, hypertension, smoking, coronary artery disease, COPD, and gender), as number and percentage (%). The continuous variables were compared across the groups using Student’s t-test or the Mann–Whitney U test. The categorical variables were compared using the Chi-square test or Fisher’s exact test. A comparison of the echocardiographic variables at admission and follow-up was performed using paired Student’s t-test or the Wilcoxon test. To determine the independent predictors of CO cardiotoxicity, multivariate logistic regression analysis was conducted by including peak troponin-I, body mass index (BMI), and GLS. Receiver operating characteristics (ROCs) curve analysis was performed to predict the cutoff value of GLS, GCS, and peak troponin-I. p 0.31 ng/mL with sensitivity of 87.5% and specificity of 41.7% (AUC = 0.656; 95% CI 0.535–0.764; p < 0.001) as obtained by ROC curve analyses (Fig. 2). To find the predictors of cardiotoxicity, multivariate logistic regression analysis was conducted by including peak troponin-I, BMI, and GLS. GLS (p ≤ 0.001; OR 1.731; 95% CI 1.313–2.281) and BMI (p ≤ 0.008; OR 1.750; 95% CI 0.606–0.929) were found as independent predictors of cardiotoxicity.
Table 3 Admission, follow-up, and control levels of strain values and left ventricular ejection fraction
Discussion It is well established that CO poisoning impairs echocardiographic parameters. However, conventional echocardiography may be insufficient for demonstrating mildly impaired LV systolic function. Our study demonstrated that impaired LV function that cannot be demonstrated using conventional echocardiography may be demonstrated using speckle tracking echocardiography. To the best of our knowledge, this is the first study to use speckle tracking echocardiography for this purpose. Both GLS and GCS were seen to be significantly impaired during the acute phase of CO poisoning compared with the mean follow-up measurements. Numerous mechanisms may play a role in cardiac dysfunction in CO poisoning. CO has approximately 30–60 times higher affinity to myoglobin and cytochrome-C oxidase compared with oxygen. When CO binds to these intracellular proteins, the heart’s capacity to use oxygen is impaired. When insufficient oxygen supply is added, cardiac dysfunction, also called stunned myocardium-like syndrome, develops [13]. Energy production and mitochondrial function recover after COHb levels decrease. Echocardiography plays a crucial role in identifying LV dysfunction in daily clinical practice. LVEF is calculated by using biplane LV end-diastolic and end-systolic volumes; however, the calculated LVEF may not truly represent LV systolic function in specific cardiac diseases or when subtle LV dysfunction is present. 2D speckle tracking echocardiography enables the assessment of myocardial strain, thereby providing detailed information on global and regional LV deformation. This is of particular interest when subtle LV systolic dysfunction is present despite preserved LVEF [14]. In this study, we applied speckle tracking echocardiography to assess LV function and to understand the process of impairment of LV function in patients with CO poisoning. In our study, LV systolic function was evaluated using the biplane Simpson’s method, and two groups were obtained: Parameters Admission
All patients (n = 72)
GLS GCS LVEF Group 1 (LVEF -19.1 Sensitivity
Sensitivity
60
GCS
40
>-17.9
20
Troponin-I 0 0
20
40
60
80
100
>0.31
100-Specificity
Fig. 2 Receiver operating characteristics curve of GLS, GCS, and troponin-I for prediction of cardiotoxicity. GCS global circumferential strain; GLS global longitudinal strain; ROC receiver operating characteristic; CI confidence interval
(mean − 23.3%) [15]. Obviously, there are differences in normal values in various studies. In our study, 35 healthy individuals were evaluated using speckle tracking echocardiography to calculate mean strain levels and obtained normal strain levels. Normal GLS and GCS values were calculated as − 21.9 ± 1.7 and − 22.2 ± 1.1, respectively. The strain levels in the LV dysfunction group were found to be far lower than normal. In preserved LVEF patients with CO poisoning, strain levels were lower than those calculated for the control group. Although our baseline normal values for GLS and GCS were slightly higher than those obtained in other studies, our primary purpose was to evaluate the difference in these values between admission and followup measurements. The significant difference between these
values could potentially be indicative of subtle LV systolic dysfunction. Based on these findings, we believe that speckle tracking echocardiography is a more specific technique than Simpson’s method to reveal subtle LV systolic dysfunction in CO poisoning cases. On the other hand, among patients with preserved LVEF, impaired GLS and GCS levels were found even if CO poisoning was mild in severity. Many reasons explain the increased sensitivity of LS compared with LVEF in the detection of CO cardiotoxicity. Subclinical LV impairment may be identified by reduced longitudinal function probably because subendocardial fibers are most susceptible to injury [16]. In cardiotoxicity studies with chemotherapeutics, subendocardial myofibrils dominating the LV longitudinal
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mechanics were seen to be more susceptible to toxicity, and GLS was impaired in the absence of LVEF impairment [17]. One opinion on this topic is that the heart was relatively unaffected mid-myocardial and epicardial mechanical function, thereby maintaining normal overall LV function, at least in the early stage [18]. According to the latest international guidelines, HBOT should be used in all patients with severe CO poisoning. The severity is assessed on indicators of organ damage rather than simply on COHb levels [10]. Troponin, CK-MB, ECG, and conventional echocardiography are used for evaluating the cardiac effects of CO poisoning; however, there is still no consensus on how to determine the treatment strategy and how to predict myocardial effects [19]. The biplane Simpson’s method that relies on LV end-diastolic and end-systolic volume measurements, myocardial performance index, or Doppler-based echocardiography measurements may not be sufficient for early prediction of subclinical dysfunction [20]. The fact that previous echocardiography studies with these methods yielded different cardiac dysfunction ratios may be supportive of our standpoint [4, 5, 21, 22]. Our study demonstrated that decreases in LS and CS values were well predictive and increases in troponin-I levels were moderately predictive of CO cardiotoxicity. When we compared troponin-I and strain levels, speckle tracking echocardiography was a better predictor. Based on these results, it can be concluded that any individual who is exposed to CO poisoning and who has clinical manifestations has affected cardiac functions. In such situations, if HBOT is available, we believe that it would be useful to refer the patient for early HBOT. Limitations The fact that patients were not able to definitely describe the duration of CO exposure may be a confounder in time-based evaluations of cardiac effects. In addition, lack of exact information on previous LV systolic function or status of coronary arteries of patients exposed to CO poisoning may alter the strain values.
Conclusions Our study demonstrates the potential of using systolic strain values obtained using 2D speckle tracking echocardiography in determining cardiotoxicity due to CO poisoning. It also showed that almost all patients exposed to CO poisoning had LV dysfunction ranging from mild to severe. As this is considered organ damage, if possible, all patients exposing to CO poisoning should be treated with HBOT. Speckle tracking echocardiography has the potential of demonstrating subtle LV systolic dysfunction even in patients with
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preserved EF. In clinical practice, this finding suggests that all CO poisoning patients could benefit from early HBOT. Compliance with Ethical Standards Conflict of interest The authors have no conflict of interest.
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