International Journal of Cardiology 177 (2014) 1108–1110
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Are there differences between Takotsubo cardiomyopathy and neurogenic stunned myocardium? A prospective observational study Joji Inamasu a,⁎,1, Eiichi Watanabe b,2, Kentaro Okuda b,3, Tadashi Kumai a,4, Keiko Sugimoto c,5, Yukio Ozaki b,6, Yuichi Hirose a,7 a b c
Department of Neurosurgery, Fujita Health University School of Medicine, Toyoake, Japan Department of Cardiology, Fujita Health University School of Medicine, Toyoake, Japan Department of Laboratory Medicine, Fujita Health University School of Medical Technology, Toyoake, Japan
a r t i c l e
i n f o
Article history: Received 11 August 2014 Accepted 14 August 2014 Available online 23 August 2014 Keywords: Catecholamine Echocardiography Electrocardiogram Neurogenic stunned myocardium Takotsubo cardiomyopathy
Many similarities have been noted between Takotsubo cardiomyopathy (TCM) and neurogenic stunned myocardium (NSM): both exhibit characteristic echocardiographic/electrocardiographic findings, and sympathetic over-activity is implicated as a common etiological mechanism [1,2]. In this single-center, prospective observational study, we aimed to clarify the potential differences between TCM and NSM by
⁎ Corresponding author at: Department of Neurosurgery, Fujita Health University School of Medicine, 1-98 Kutsukake, Toyoake 470-1192, Japan. Tel.: +81 562 93 9153; fax: +81 562 93 3118. E-mail address: [email protected] (J. Inamasu). 1 Joji Inamasu, MD, PhD, FACS takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 2 Eiichi Watanabe, MD, PhD takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 3 Kentaro Okuda, MD, PhD takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 4 Tadashi Kumai, MD takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 5 Keiko Sugimoto, PhD takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 6 Yukio Ozaki, MD, PhD, FESC takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 7 Yuichi Hirose, MD, PhD takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
http://dx.doi.org/10.1016/j.ijcard.2014.08.084 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
comparing their neurochemical, echocardiographic, and electrocardiographic profiles. After approval by our institutional internal review board, we prospectively assessed the following parameters in aneurysmal subarachnoid hemorrhage (SAH) patients who presented within 24 h of onset: blood levels of catecholamines (epinephrine/norepinephrine) and other cardiac biomarkers (troponin I, B-type natriuretic peptide, and creatine kinase isoenzyme), transthoracic echocardiography (TTE), and ECG. Similarly, TCM patients underwent routine measurement of plasma catecholamines and other cardiac biomarkers within 24 h of onset. The diagnosis of TCM/NSM was based on the Proposed Mayo Clinic Criteria [3]. Standard Doppler assessment of diastolic function was performed according to the American Society of Echocardiography guidelines [4]. Early diastolic (E) wave velocities and atrial (A) wave velocities, and the E wave deceleration time were measured using pulse wave Doppler recording. Septal and lateral mitral annular early diastolic velocities (E′) were measured from an apical 4-chamber view using offline color tissue Doppler images, and the E/ E′ ratio was calculated [4]. For the evaluation of ventricular wall motion abnormality (WMA), the American Society of Echocardiography's 16 segment model and Regional Wall Motion Score Index (RWMSI) were used [4,5]. The frequencies of WMA were illustrated by the 16 segment model, and those in corresponding segments were compared between the two groups. Moreover, the frequencies of ST-segment elevation, T-wave inversion, and mean QTc interval were compared. The Fisher's exact test and Student t-test were used to compare categorical and continuous variables. Linear regression analysis was performed to evaluate the correlation between plasma epinephrine and norepinephrine levels. JMP software (SAS Institute, Cary, NC) was used for statistical analyses. Numerical data are expressed as mean ± SD, and p b 0.05 was considered statistically significant. Between January 2012 and December 2013, 19 patients were diagnosed with TCM and 12 patients with aneurysmal SAH were diagnosed with NSM. NSM group was significantly younger and presented with significantly worse consciousness level (Table 1). There were no significant intergroup differences in the physiological variables (Table 1). The plasma epinephrine levels (pg/mL) were significantly lower in TCM group (96 ± 72 vs. 392 ± 331, p = 0.007) (Fig. 1A). Similarly, the plasma norepinephrine levels (pg/mL) were significantly lower in TCM group (1015 ± 1038 vs. 2028 ± 1216, p = 0.01) (Fig. 1B). The plasma
J. Inamasu et al. / International Journal of Cardiology 177 (2014) 1108–1110 Table 1 Comparison of demographic/physiological variables and blood levels of cardiac biomarkers between Takotsubo cardiomyopathy and neurogenic stunned myocardium patients.
Age (y) Male:Female Presenting symptoms
Aneurysm locations Admission GCS scores Prior cardiac events Hypertension Hyperlipidemia Diabetes mellitus Psychiatric history Systolic BP (mm Hg) Diastolic BP (mm Hg) Heart rate (bpm) Pulmonary edema Troponin I (ng/mL) BNP (pg/mL) CK-MB (ng/mL)
TCM (n = 19)
NSM (n = 12)
p-Value
71.7 ± 7.6 8:11 Chest pain 8 Dyspnea 7 Dizziness 4 N/A 14.7 ± 0.7 8 (42%) 10 (53%) 6 (32%) 8 (42%) 2 (11%) 149 ± 32 83 ± 19 103 ± 31 4/19 (21%) 2.92 ± 4.61 460.2 ± 575.1 33.8 ± 46.1
57.5 ± 13.7 6:6 Headache 5 Altered mental status 7
b0.01* 0.95 N/A
ACoA 4, ICA 2, MCA 2, VA 4 8.2 ± 2.7 0 6 (50%) 2 (%) 2 (17%) 0 166 ± 58 91 ± 35 93 ± 32 6/12 (50%) 1.75 ± 3.22 252.4 ± 305.1 25.8 ± 18.0
N/A b0.001** 0.03*** 0.82 0.67 0.25 0.51 0.31 0.37 0.39 0.20 0.40 0.30 0.59
ACoA: anterior communicating artery; BNP: B-type natriuretic peptide; BP: blood pressure; CK-MB: creatine kinase MB isozyme; GCS: Glasgow Coma Scale; ICA: internal carotid artery; MCA: middle cerebral artery; NA: not applicable; NSM: neurogenic stunned myocardium; TCM: Takotsubo cardiomyopathy; VA: vertebral artery. *, **, ***: statistically significant.
epinephrine and norepinephrine levels were both positively correlated in TCM (R = 0.70, p = 0.0007) and in NSM group (R = 0.64, p = 0.03) (Fig. 1C, D). There were no significant intergroup differences in the other biomarker levels (Table 1). The E/E′ ratio was significantly higher in TCM group (17.7 ± 7.5 vs. 12.2 ± 4.6, p = 0.04) (Table 2). There were no significant differences
1109
Table 2 Comparison of echocardiographic and electrocardiographic parameters between Takotsubo cardiomyopathy and neurogenic stunned myocardium patients.
LVEF (%) LVIDd (mm) LVIDs (mm) LVMI (g/m2) E (m/s) A (m/s) E/A E′ (m/s) E/E′ DcT (ms) RWMSI ST-segment elevation T-wave inversion QTc (ms)
TCM (n = 19)
NSM (n = 12)
p-Value
42.6 ± 9.2 45.9 ± 7.7 34.2 ± 8.4 126.1 ± 37.7 78.2 ± 26.7 86.2 ± 29.3 1.02 ± 0.60 4.89 ± 1.91 17.7 ± 7.5 173.6 ± 47.5 1.67 ± 0.31 12/19 (63%) 13/19 (68%) 479 ± 4
44.2 ± 9.1 45.0 ± 7.9 37.0 ± 8.1 108.5 ± 46.3 59.8 ± 20.6 73.5 ± 22.0 0.88 ± 0.39 5.30 ± 1.95 12.2 ± 4.6 172.7 ± 40.2 1.71 ± 0.34 6/12 (50%) 3/12 (25%) 468 ± 4
0.65 0.74 0.30 0.33 0.07 0.26 0.53 0.58 0.04* 0.96 0.67 0.73 0.03** 0.50
DcT: deceleration time; LVEF: left ventricular ejection fraction; LVIDd: left ventricular internal dimension, diastole; LVIDs: left ventricular internal dimension, systole; LVMI: left ventricular mass index; NSM: neurogenic stunned myocardium; RWMSI: Regional Wall Motion Score Index; TCM: Takotsubo cardiomyopathy. *, **: statistically significant.
in the other TTE parameters. Comparison of the 16 segment model showed no significant differences in the frequency of regional WMA (Fig. 2). The frequency of T-wave inversion was significantly higher in TCM group (68% vs. 25%, p = 0.03) (Table 2). By contrast, there were no significant intergroup differences in the frequency of ST-segment elevation or mean QTc interval (Table 2). This study revealed several differences between TCM and NSM. In neurochemical perspective, substantial differences in the epinephrine/ norepinephrine correlation coefficient were observed (Fig. 1C, D). Plasma epinephrine levels increase markedly and to a greater extent than norepinephrine levels in response to various stresses [6]. The greater
Fig. 1. The plasma epinephrine levels (pg/mL) were 96 ± 72 for Takotsubo cardiomyopathy (TCM) and 392 ± 331 for neurogenic stunned myocardium (NSM) group (A). The difference was statistically significant (p = 0.007*). The plasma norepinephrine levels (pg/mL) were 1015 ± 1038 for TCM and 2028 ± 1216 for NSM (B). The difference was statistically significant (p = 0.01**). Linear regression analysis revealing that the plasma epinephrine and norepinephrine levels were positively correlated in TCM group (R = 0.70, p = 0.0007) (C). The plasma epinephrine and norepinephrine levels were also positively correlated in NSM group (R = 0.64, p = 0.03) (D).
1110
J. Inamasu et al. / International Journal of Cardiology 177 (2014) 1108–1110
was significantly more likely to induce typical TCM-like cardiac dysfunction [8]. Most echocardiographic parameters were comparable except the E/ E′ ratio (Table 2). The higher E/E′ ratio in TCM group indicates the presence of more severe diastolic dysfunction [9]. That difference could be explained by differences in demographics: TCM patients were significantly older and more likely to have had prior cardiac events, and stiffened myocardium in that group might have resulted in worse diastolic dysfunction and a higher E/E′ ratio. On the other hand, the degree of systolic dysfunction, the degree of myocardial injury, and spatial RWMA distribution were similar between the two groups. The lower frequency of T-wave inversion in NSM group without significant difference in STsegment elevation may be explained by the general propensity for SAH patients to present earlier after onset: conversion from ST-segment elevation to T-wave inversion might have not occurred in most NSM patients by the time of their arrival [10]. There are several limitations to this study. First, timing of follow-up examinations was not standardized and we were unable to perform a chronological evaluation. Second, the number of patients was small: given that both disorders have low incidences making it difficult to accumulating adequate samples, it is important to establish national/ international registries. Finally, because of the short half-life of epinephrine, the epinephrine/norepinephrine coefficient may vary substantially with the timing of blood collection [7]. In conclusion, more prominent diastolic dysfunction and more frequent T-wave inversion in TCM group may have resulted from demographic differences. While plasma catecholamine levels were raised in greater magnitudes in NSM group, it remains unclear whether that difference explains the echocardiographic/electrocardiographic differences. The authors certify that they comply with the principles of Ethical Publishing in the International Journal of Cardiology. Disclosure The first author (JI) received a research grant from the Japan Brain Foundation. References Fig. 2. Comparison of the 16 segment model between Takotsubo cardiomyopathy (A) and neurogenic stunned myocardium group (B) revealing that there were no significant differences in the frequency of regional wall motion abnormality in any of the corresponding segments.
increase of epinephrine relative to norepinephrine in NSM group may be reasonable considering the greater physiological stress in SAH patients. In the pathogenesis of TCM, epinephrine has been considered to play a pivotal role: the difference in distribution of β1/β2adrenoceptors between the apical and basal myocardium is attributed to the greater contractile response to epinephrine in the apical myocardium with subsequent apical stunning [7]. By contrast, the etiological role of epinephrine in NSM is less clear: studies on aneurysmal SAH implicate norepinephrine, not epinephrine, as the main causative agent [5]. The greater epinephrine/norepinephrine correlation coefficient in NSM group (Fig. 1D) may not signify that epinephrine is the primary cause of SAH-induced WMA. Rather, the current results may simply indicate that differences in the catecholamine levels and adrenoceptor subtype affinity may not be as decisive in the pathogenesis of WMA: a recent experimental study demonstrated that norepinephrine
[1] Pilgrim TM, Wyss TR. Takotsubo cardiomyopathy or transient left ventricular apical ballooning syndrome: A systematic review. Int J Cardiol 2008;124:283–92. [2] Bielecka-Dabrowa A, Mikhailidis DP, Hannam S, et al. Takotsubo cardiomyopathy: the current state of knowledge. Int J Cardiol 2010;142:120–5. [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] Tanabe M, Crago EA, Suffoletto MS, et al. Relation of elevation in cardiac troponin I to clinical severity, cardiac dysfunction, and pulmonary congestion in patients with subarachnoid hemorrhage. Am J Cardiol 2008;102:1545–50. [5] Sugimoto K, Inamasu J, Hirose Y, et al. The role of norepinephrine and estradiol in the pathogenesis of cardiac wall motion abnormality associated with subarachnoid hemorrhage. Stroke 2012;43:1897–903. [6] Goldstein DS, Eisenhofer G, Kopin IJ. Sources and significance of plasma levels of catechols and their metabolites in humans. J Pharmacol Exp Ther 2003;305:800–11. [7] Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE. Stress (Takotsubo) cardiomyopathy: a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med 2008;5:22–9. [8] Redfors B, Ali A, Shao Y, Lundgren J, Gan LM, Omerovic E. Different catecholamines induce different patterns of takotsubo-like cardiac dysfunction in an apparently afterload dependent manner. Int J Cardiol 2014;174:330–6. [9] Medeiros K, O'Connor MJ, Baicu CF, et al. Systolic and diastolic mechanics in stress cardiomyopathy. Circulation 2014;129:1659–67. [10] Madias JE. Plausible mechanisms of the rapid conversion of ST-segment elevation to T-wave inversion in Takotsubo syndrome. Int J Cardiol 2013;168:4593–5.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Are there differences between Takotsubo cardiomyopathy and neurogenic stunned myocardium? A prospective observational study Joji Inamasu a,⁎,1, Eiichi Watanabe b,2, Kentaro Okuda b,3, Tadashi Kumai a,4, Keiko Sugimoto c,5, Yukio Ozaki b,6, Yuichi Hirose a,7 a b c
Department of Neurosurgery, Fujita Health University School of Medicine, Toyoake, Japan Department of Cardiology, Fujita Health University School of Medicine, Toyoake, Japan Department of Laboratory Medicine, Fujita Health University School of Medical Technology, Toyoake, Japan
a r t i c l e
i n f o
Article history: Received 11 August 2014 Accepted 14 August 2014 Available online 23 August 2014 Keywords: Catecholamine Echocardiography Electrocardiogram Neurogenic stunned myocardium Takotsubo cardiomyopathy
Many similarities have been noted between Takotsubo cardiomyopathy (TCM) and neurogenic stunned myocardium (NSM): both exhibit characteristic echocardiographic/electrocardiographic findings, and sympathetic over-activity is implicated as a common etiological mechanism [1,2]. In this single-center, prospective observational study, we aimed to clarify the potential differences between TCM and NSM by
⁎ Corresponding author at: Department of Neurosurgery, Fujita Health University School of Medicine, 1-98 Kutsukake, Toyoake 470-1192, Japan. Tel.: +81 562 93 9153; fax: +81 562 93 3118. E-mail address: [email protected] (J. Inamasu). 1 Joji Inamasu, MD, PhD, FACS takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 2 Eiichi Watanabe, MD, PhD takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 3 Kentaro Okuda, MD, PhD takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 4 Tadashi Kumai, MD takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 5 Keiko Sugimoto, PhD takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 6 Yukio Ozaki, MD, PhD, FESC takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 7 Yuichi Hirose, MD, PhD takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
http://dx.doi.org/10.1016/j.ijcard.2014.08.084 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
comparing their neurochemical, echocardiographic, and electrocardiographic profiles. After approval by our institutional internal review board, we prospectively assessed the following parameters in aneurysmal subarachnoid hemorrhage (SAH) patients who presented within 24 h of onset: blood levels of catecholamines (epinephrine/norepinephrine) and other cardiac biomarkers (troponin I, B-type natriuretic peptide, and creatine kinase isoenzyme), transthoracic echocardiography (TTE), and ECG. Similarly, TCM patients underwent routine measurement of plasma catecholamines and other cardiac biomarkers within 24 h of onset. The diagnosis of TCM/NSM was based on the Proposed Mayo Clinic Criteria [3]. Standard Doppler assessment of diastolic function was performed according to the American Society of Echocardiography guidelines [4]. Early diastolic (E) wave velocities and atrial (A) wave velocities, and the E wave deceleration time were measured using pulse wave Doppler recording. Septal and lateral mitral annular early diastolic velocities (E′) were measured from an apical 4-chamber view using offline color tissue Doppler images, and the E/ E′ ratio was calculated [4]. For the evaluation of ventricular wall motion abnormality (WMA), the American Society of Echocardiography's 16 segment model and Regional Wall Motion Score Index (RWMSI) were used [4,5]. The frequencies of WMA were illustrated by the 16 segment model, and those in corresponding segments were compared between the two groups. Moreover, the frequencies of ST-segment elevation, T-wave inversion, and mean QTc interval were compared. The Fisher's exact test and Student t-test were used to compare categorical and continuous variables. Linear regression analysis was performed to evaluate the correlation between plasma epinephrine and norepinephrine levels. JMP software (SAS Institute, Cary, NC) was used for statistical analyses. Numerical data are expressed as mean ± SD, and p b 0.05 was considered statistically significant. Between January 2012 and December 2013, 19 patients were diagnosed with TCM and 12 patients with aneurysmal SAH were diagnosed with NSM. NSM group was significantly younger and presented with significantly worse consciousness level (Table 1). There were no significant intergroup differences in the physiological variables (Table 1). The plasma epinephrine levels (pg/mL) were significantly lower in TCM group (96 ± 72 vs. 392 ± 331, p = 0.007) (Fig. 1A). Similarly, the plasma norepinephrine levels (pg/mL) were significantly lower in TCM group (1015 ± 1038 vs. 2028 ± 1216, p = 0.01) (Fig. 1B). The plasma
J. Inamasu et al. / International Journal of Cardiology 177 (2014) 1108–1110 Table 1 Comparison of demographic/physiological variables and blood levels of cardiac biomarkers between Takotsubo cardiomyopathy and neurogenic stunned myocardium patients.
Age (y) Male:Female Presenting symptoms
Aneurysm locations Admission GCS scores Prior cardiac events Hypertension Hyperlipidemia Diabetes mellitus Psychiatric history Systolic BP (mm Hg) Diastolic BP (mm Hg) Heart rate (bpm) Pulmonary edema Troponin I (ng/mL) BNP (pg/mL) CK-MB (ng/mL)
TCM (n = 19)
NSM (n = 12)
p-Value
71.7 ± 7.6 8:11 Chest pain 8 Dyspnea 7 Dizziness 4 N/A 14.7 ± 0.7 8 (42%) 10 (53%) 6 (32%) 8 (42%) 2 (11%) 149 ± 32 83 ± 19 103 ± 31 4/19 (21%) 2.92 ± 4.61 460.2 ± 575.1 33.8 ± 46.1
57.5 ± 13.7 6:6 Headache 5 Altered mental status 7
b0.01* 0.95 N/A
ACoA 4, ICA 2, MCA 2, VA 4 8.2 ± 2.7 0 6 (50%) 2 (%) 2 (17%) 0 166 ± 58 91 ± 35 93 ± 32 6/12 (50%) 1.75 ± 3.22 252.4 ± 305.1 25.8 ± 18.0
N/A b0.001** 0.03*** 0.82 0.67 0.25 0.51 0.31 0.37 0.39 0.20 0.40 0.30 0.59
ACoA: anterior communicating artery; BNP: B-type natriuretic peptide; BP: blood pressure; CK-MB: creatine kinase MB isozyme; GCS: Glasgow Coma Scale; ICA: internal carotid artery; MCA: middle cerebral artery; NA: not applicable; NSM: neurogenic stunned myocardium; TCM: Takotsubo cardiomyopathy; VA: vertebral artery. *, **, ***: statistically significant.
epinephrine and norepinephrine levels were both positively correlated in TCM (R = 0.70, p = 0.0007) and in NSM group (R = 0.64, p = 0.03) (Fig. 1C, D). There were no significant intergroup differences in the other biomarker levels (Table 1). The E/E′ ratio was significantly higher in TCM group (17.7 ± 7.5 vs. 12.2 ± 4.6, p = 0.04) (Table 2). There were no significant differences
1109
Table 2 Comparison of echocardiographic and electrocardiographic parameters between Takotsubo cardiomyopathy and neurogenic stunned myocardium patients.
LVEF (%) LVIDd (mm) LVIDs (mm) LVMI (g/m2) E (m/s) A (m/s) E/A E′ (m/s) E/E′ DcT (ms) RWMSI ST-segment elevation T-wave inversion QTc (ms)
TCM (n = 19)
NSM (n = 12)
p-Value
42.6 ± 9.2 45.9 ± 7.7 34.2 ± 8.4 126.1 ± 37.7 78.2 ± 26.7 86.2 ± 29.3 1.02 ± 0.60 4.89 ± 1.91 17.7 ± 7.5 173.6 ± 47.5 1.67 ± 0.31 12/19 (63%) 13/19 (68%) 479 ± 4
44.2 ± 9.1 45.0 ± 7.9 37.0 ± 8.1 108.5 ± 46.3 59.8 ± 20.6 73.5 ± 22.0 0.88 ± 0.39 5.30 ± 1.95 12.2 ± 4.6 172.7 ± 40.2 1.71 ± 0.34 6/12 (50%) 3/12 (25%) 468 ± 4
0.65 0.74 0.30 0.33 0.07 0.26 0.53 0.58 0.04* 0.96 0.67 0.73 0.03** 0.50
DcT: deceleration time; LVEF: left ventricular ejection fraction; LVIDd: left ventricular internal dimension, diastole; LVIDs: left ventricular internal dimension, systole; LVMI: left ventricular mass index; NSM: neurogenic stunned myocardium; RWMSI: Regional Wall Motion Score Index; TCM: Takotsubo cardiomyopathy. *, **: statistically significant.
in the other TTE parameters. Comparison of the 16 segment model showed no significant differences in the frequency of regional WMA (Fig. 2). The frequency of T-wave inversion was significantly higher in TCM group (68% vs. 25%, p = 0.03) (Table 2). By contrast, there were no significant intergroup differences in the frequency of ST-segment elevation or mean QTc interval (Table 2). This study revealed several differences between TCM and NSM. In neurochemical perspective, substantial differences in the epinephrine/ norepinephrine correlation coefficient were observed (Fig. 1C, D). Plasma epinephrine levels increase markedly and to a greater extent than norepinephrine levels in response to various stresses [6]. The greater
Fig. 1. The plasma epinephrine levels (pg/mL) were 96 ± 72 for Takotsubo cardiomyopathy (TCM) and 392 ± 331 for neurogenic stunned myocardium (NSM) group (A). The difference was statistically significant (p = 0.007*). The plasma norepinephrine levels (pg/mL) were 1015 ± 1038 for TCM and 2028 ± 1216 for NSM (B). The difference was statistically significant (p = 0.01**). Linear regression analysis revealing that the plasma epinephrine and norepinephrine levels were positively correlated in TCM group (R = 0.70, p = 0.0007) (C). The plasma epinephrine and norepinephrine levels were also positively correlated in NSM group (R = 0.64, p = 0.03) (D).
1110
J. Inamasu et al. / International Journal of Cardiology 177 (2014) 1108–1110
was significantly more likely to induce typical TCM-like cardiac dysfunction [8]. Most echocardiographic parameters were comparable except the E/ E′ ratio (Table 2). The higher E/E′ ratio in TCM group indicates the presence of more severe diastolic dysfunction [9]. That difference could be explained by differences in demographics: TCM patients were significantly older and more likely to have had prior cardiac events, and stiffened myocardium in that group might have resulted in worse diastolic dysfunction and a higher E/E′ ratio. On the other hand, the degree of systolic dysfunction, the degree of myocardial injury, and spatial RWMA distribution were similar between the two groups. The lower frequency of T-wave inversion in NSM group without significant difference in STsegment elevation may be explained by the general propensity for SAH patients to present earlier after onset: conversion from ST-segment elevation to T-wave inversion might have not occurred in most NSM patients by the time of their arrival [10]. There are several limitations to this study. First, timing of follow-up examinations was not standardized and we were unable to perform a chronological evaluation. Second, the number of patients was small: given that both disorders have low incidences making it difficult to accumulating adequate samples, it is important to establish national/ international registries. Finally, because of the short half-life of epinephrine, the epinephrine/norepinephrine coefficient may vary substantially with the timing of blood collection [7]. In conclusion, more prominent diastolic dysfunction and more frequent T-wave inversion in TCM group may have resulted from demographic differences. While plasma catecholamine levels were raised in greater magnitudes in NSM group, it remains unclear whether that difference explains the echocardiographic/electrocardiographic differences. The authors certify that they comply with the principles of Ethical Publishing in the International Journal of Cardiology. Disclosure The first author (JI) received a research grant from the Japan Brain Foundation. References Fig. 2. Comparison of the 16 segment model between Takotsubo cardiomyopathy (A) and neurogenic stunned myocardium group (B) revealing that there were no significant differences in the frequency of regional wall motion abnormality in any of the corresponding segments.
increase of epinephrine relative to norepinephrine in NSM group may be reasonable considering the greater physiological stress in SAH patients. In the pathogenesis of TCM, epinephrine has been considered to play a pivotal role: the difference in distribution of β1/β2adrenoceptors between the apical and basal myocardium is attributed to the greater contractile response to epinephrine in the apical myocardium with subsequent apical stunning [7]. By contrast, the etiological role of epinephrine in NSM is less clear: studies on aneurysmal SAH implicate norepinephrine, not epinephrine, as the main causative agent [5]. The greater epinephrine/norepinephrine correlation coefficient in NSM group (Fig. 1D) may not signify that epinephrine is the primary cause of SAH-induced WMA. Rather, the current results may simply indicate that differences in the catecholamine levels and adrenoceptor subtype affinity may not be as decisive in the pathogenesis of WMA: a recent experimental study demonstrated that norepinephrine
[1] Pilgrim TM, Wyss TR. Takotsubo cardiomyopathy or transient left ventricular apical ballooning syndrome: A systematic review. Int J Cardiol 2008;124:283–92. [2] Bielecka-Dabrowa A, Mikhailidis DP, Hannam S, et al. Takotsubo cardiomyopathy: the current state of knowledge. Int J Cardiol 2010;142:120–5. [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] Tanabe M, Crago EA, Suffoletto MS, et al. Relation of elevation in cardiac troponin I to clinical severity, cardiac dysfunction, and pulmonary congestion in patients with subarachnoid hemorrhage. Am J Cardiol 2008;102:1545–50. [5] Sugimoto K, Inamasu J, Hirose Y, et al. The role of norepinephrine and estradiol in the pathogenesis of cardiac wall motion abnormality associated with subarachnoid hemorrhage. Stroke 2012;43:1897–903. [6] Goldstein DS, Eisenhofer G, Kopin IJ. Sources and significance of plasma levels of catechols and their metabolites in humans. J Pharmacol Exp Ther 2003;305:800–11. [7] Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE. Stress (Takotsubo) cardiomyopathy: a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med 2008;5:22–9. [8] Redfors B, Ali A, Shao Y, Lundgren J, Gan LM, Omerovic E. Different catecholamines induce different patterns of takotsubo-like cardiac dysfunction in an apparently afterload dependent manner. Int J Cardiol 2014;174:330–6. [9] Medeiros K, O'Connor MJ, Baicu CF, et al. Systolic and diastolic mechanics in stress cardiomyopathy. Circulation 2014;129:1659–67. [10] Madias JE. Plausible mechanisms of the rapid conversion of ST-segment elevation to T-wave inversion in Takotsubo syndrome. Int J Cardiol 2013;168:4593–5.
