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Reduced dobutamine stress test-based coronary flow reserve in patients with Takotsubo syndrome: An innate substrate or a lingering effect?
International Journal of Cardiology 201 (2015) 174–175
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Reduced dobutamine stress test-based coronary flow reserve in patients with Takotsubo syndrome: An innate substrate or a lingering effect? John E. Madias ⁎ Icahn School of Medicine at Mount Sinai, United States Division of Cardiology, Elmhurst Hospital Center, Elmhurst, NY, United States
a r t i c l e
i n f o
Article history: Received 19 July 2015 Accepted 1 August 2015 Available online 3 August 2015 Keywords: Takotsubo syndrome Coronary flow reserve Microvascular dysfunction Dobutamine stress test Doppler echocardiography
To the Editor: Various degrees of impairment of coronary microcirculation, to its full obliteration (microvascular dysfunction [MVD]) have been associated with Takotsubo syndrome (TTS), as evaluated by sluggish coronary flow with the Thrombolysis In Myocardial Infarction frame count [1], in the presence of completely normal epicardial coronary anatomy at coronary arteriography. It is unclear whether this MVD is the cause, or part and parcel of the TTS after its inception, or a consequence of the illness. This author favors the later, but there are no clinical studies or experiments in TTS animal models exploring the phenomenon, with serial assessment of microcirculation's impairment, its onset, course and eventual resolution, to our full satisfaction. Previous work has shown a decreased coronary flow reserve (CFR) during the subacute phase of TTS, using noninvasive Doppler transthoracic echocardiography [2,4]. A dipyridamole, adenosine and cold pressor test has been employed in the invasive and non-invasive assessment of CFR in these studies [2–5], which showed MVD impairment of patients early in the course of TTS with normalization noted weeks to months of recovery. Considering that stress, emotional or physical, must be playing a role as a trigger of TTS, the study of Collste et al. [6] is intuitively appealing. ⁎ Division of Cardiology, Elmhurst Hospital Center, 79-01 Broadway, Elmhurst, NY 11373, United States. E-mail address: [email protected].
http://dx.doi.org/10.1016/j.ijcard.2015.08.019 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
Their study employed a dobutamine (a catecholamine resembling epinephrine) stress testing-based assessment of CFR in conjunction with coronary flow velocity in the left anterior descending coronary artery (LAD) by transthoracic Doppler echocardiography in 22 patients from the database of the Stockholm Myocardial Infarction with Normal Coronaries study, at a mean of ~20 months (N 6 months) after the index episode of TTS, and 22 age-, and gender-matched normal controls. Further support for the underlying hypothesis of the authors [6] is the fact that routinely employed dobutamine stress testing for diagnostic purposes, has led to TTS in some patients [7–15]. Collste et al. [6] found that “CFR at low-dose dobutamine (10 μg/kg/min) was significantly lower in the TTS group compared with controls, 1.51 and 1.72, respectively (p = 0.017)”, while, “at high-dose dobutamine (40 μg/kg/min), CFR was 1.95 and 2.21 in the TSC group and controls, respectively (p = 0.098)” and they concluded that they “could not confirm that the catecholamine dobutamine induced MVD in patients with TTS”, and “that the role of MVD in TTS needs to be further explored”. This is the first study to employ the assessment of dobutamine stress test-based CFR in patients with TTS, but the issue explored needs further study. The authors have discussed the limitations of their work: small sample size, higher rate of treatment with β-blockers, angiotensin converting enzyme inhibitors and calcium blockers, smoking, and hypertension (although p = 0.12) in the TTS cohort rather than the normal controls, suggestive of synergistic influences above the status of prior TTS. Also there is a nonsignificant difference in the rise of CFR in the 2 cohorts with a higher dobutamine dose, while the lower dobutamine dose led to a statistically significant lower CFR in the TTS cohort than the normal control cohort, which the authors attributed to a larger variation of CFR means in the normal controls with the larger dobutamine dose. It is conceivable that different CFR results are expected with the dobutamine stress test, or cold pressor test, or dipyridamole or adenosine in the convalescence phase of TTS, and the authors alluded to such possibilities [6]. However with the data at hand from this investigation one wonders whether there is a persistent decrease in CFR in patients many months after an index episode of TTS, at least when this is assessed with a dobutamine stress test and transthoracic Doppler echocardiography of LAD coronary flows. Is this due to an innate inclination (genetic and/or acquired) for MVD on exposure to catecholamines (epinephrine, norepinephrine, and dobutamine)? Is this a lingering effect of MVD which is destined to normalize after a few more months in
Letter to the Editor
patients with TTS? In reference to this, and since the dobutamine stress test was done at a mean 619 ± 297 days after the index episode of TTS [6], one wonders whether there was a relationship between CFR at low or high dobutamine dose and the time interval between the inception of the illness and the performance of the dobutamine stress test. Finally the authors of this study [6] could provide us with valuable insights if they repeat the dobutamine stress test in their patients a year from the previous test in all, or some of their 22 patients with TTS, with or without a study of the normal controls.
Conflicts of interest None.
References [1] N. Khalid, I. Iqbal, R. Coram, T. Raza, I. Fahsah, S. Ikram, Thrombolysis in myocardial infarction frame count in Takotsubo cardiomyopathy, Int. J. Cardiol. 191 (2015) 107–108. [2] P. Meimoun, D. Malaquin, S. Sayah, et al., The coronary flow reserve is transiently impaired in Tako-tsubo cardiomyopathy: a prospective study using serial Doppler transthoracic echocardiography, J. Am. Soc. Echocardiogr. 21 (2008) 72–77. [3] S. Yanagi, K. Nagae, K. Yoshida, et al., Evaluation of coronary flow reserve using Doppler guide wire in patients with ampulla cardiomyopathy: three case reports, J. Cardiol. 39 (2002) 305–312. [4] T. Kume, T. Akasaka, T. Kawamoto, et al., Assessment of coronary microcirculation in patients with Takotsubo-like left ventricular dysfunction, Circ. J. 69 (2005) 934–939.
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[5] F. Rigo, R. Sicari, R. Citro, et al., Diffuse, marked, reversible impairment in coronary microcirculation in stress cardiomyopathy: a Doppler transthoracic echo study, Ann. Med. 41 (2009) 462–470. [6] O. Collste, P. Tornvall, M. Alam, M. Frick, Coronary flow reserve during dobutamine stress in Takotsubo stress cardiomyopathy, BMJ Open 5 (7) (Jul 16 2015) e007671. [7] S.D. Brewington, A.A. Abbas, S.R. Dixon, C.L. Grines, W.W. O'Neill, Reproducible microvascular dysfunction with dobutamine infusion in Takotsubo cardiomyopathy presenting with ST segment elevation, Catheter. Cardiovasc. Interv. 68 (2006) 769–774. [8] J. Cherian, S. Kothari, D. Angelis, A. Atef, B. Downey, J. Kirkpatrick Jr., Atypical Takotsubo cardiomyopathy: dobutamine-precipitated apical ballooning with left ventricular outflow tract obstruction, Tex. Heart Inst. J. 35 (2008) 73–75. [9] R. Margey, P. Diamond, H. McCann, D. Sugrue, Dobutamine stress echo-induced apical ballooning (Takotsubo) syndrome, Eur. J. Echocardiogr. 10 (2009) 395–399. [10] B. Uznańska, M. Plewka, K. Wierzbowska-Drabik, L. Chrzanowski, J.D. Kasprzak, Early prediction of ventricular recovery in Takotsubo syndrome using stress and contrast echocardiography, Med. Sci. Monit. 15 (2009) CS89–CS94. [11] F.J. Vasconcelos Filho, C.A. Gomes, O.A. Queiroz, J.E. Barreto, Dobutamine stress echocardiography-induced broken heart syndrome (Takotsubo syndrome), Arq. Bras. Cardiol. 93 (2009) e5–e7. [12] O. Sonmez, C. Duman, M.A. Duzenli, M. Tokac, Special attention for elderly women: atypical left ventricular apical ballooning syndrome induced by dobutamine stress test: a case report, J. Am. Geriatr. Soc. 57 (2009) 1735–1736. [13] C. Cadeddu, S. Nocco, F. Cadeddu, M., et al., Inverted Takotsubo cardiomyopathy induced by dobutamine stress echocardiography with atypical presentation, Case Rep. Cardiol. 2011 (2011) 413645. [14] A.M. Arias, P.F. Oberti, R. Pizarro, et al., Dobutamine-precipitated Takotsubo cardiomyopathy mimicking acute myocardial infarction: a multimodality image approach, Circulation 124 (2011) e312–e315. [15] J.E. Madias, Dobutamine stress echocardiography and Takotsubo syndrome: could milder forms of this pathology confound the diagnostic value of the test? Echocardiography 30 (2013) 737.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Reduced dobutamine stress test-based coronary flow reserve in patients with Takotsubo syndrome: An innate substrate or a lingering effect? John E. Madias ⁎ Icahn School of Medicine at Mount Sinai, United States Division of Cardiology, Elmhurst Hospital Center, Elmhurst, NY, United States
a r t i c l e
i n f o
Article history: Received 19 July 2015 Accepted 1 August 2015 Available online 3 August 2015 Keywords: Takotsubo syndrome Coronary flow reserve Microvascular dysfunction Dobutamine stress test Doppler echocardiography
To the Editor: Various degrees of impairment of coronary microcirculation, to its full obliteration (microvascular dysfunction [MVD]) have been associated with Takotsubo syndrome (TTS), as evaluated by sluggish coronary flow with the Thrombolysis In Myocardial Infarction frame count [1], in the presence of completely normal epicardial coronary anatomy at coronary arteriography. It is unclear whether this MVD is the cause, or part and parcel of the TTS after its inception, or a consequence of the illness. This author favors the later, but there are no clinical studies or experiments in TTS animal models exploring the phenomenon, with serial assessment of microcirculation's impairment, its onset, course and eventual resolution, to our full satisfaction. Previous work has shown a decreased coronary flow reserve (CFR) during the subacute phase of TTS, using noninvasive Doppler transthoracic echocardiography [2,4]. A dipyridamole, adenosine and cold pressor test has been employed in the invasive and non-invasive assessment of CFR in these studies [2–5], which showed MVD impairment of patients early in the course of TTS with normalization noted weeks to months of recovery. Considering that stress, emotional or physical, must be playing a role as a trigger of TTS, the study of Collste et al. [6] is intuitively appealing. ⁎ Division of Cardiology, Elmhurst Hospital Center, 79-01 Broadway, Elmhurst, NY 11373, United States. E-mail address: [email protected].
http://dx.doi.org/10.1016/j.ijcard.2015.08.019 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
Their study employed a dobutamine (a catecholamine resembling epinephrine) stress testing-based assessment of CFR in conjunction with coronary flow velocity in the left anterior descending coronary artery (LAD) by transthoracic Doppler echocardiography in 22 patients from the database of the Stockholm Myocardial Infarction with Normal Coronaries study, at a mean of ~20 months (N 6 months) after the index episode of TTS, and 22 age-, and gender-matched normal controls. Further support for the underlying hypothesis of the authors [6] is the fact that routinely employed dobutamine stress testing for diagnostic purposes, has led to TTS in some patients [7–15]. Collste et al. [6] found that “CFR at low-dose dobutamine (10 μg/kg/min) was significantly lower in the TTS group compared with controls, 1.51 and 1.72, respectively (p = 0.017)”, while, “at high-dose dobutamine (40 μg/kg/min), CFR was 1.95 and 2.21 in the TSC group and controls, respectively (p = 0.098)” and they concluded that they “could not confirm that the catecholamine dobutamine induced MVD in patients with TTS”, and “that the role of MVD in TTS needs to be further explored”. This is the first study to employ the assessment of dobutamine stress test-based CFR in patients with TTS, but the issue explored needs further study. The authors have discussed the limitations of their work: small sample size, higher rate of treatment with β-blockers, angiotensin converting enzyme inhibitors and calcium blockers, smoking, and hypertension (although p = 0.12) in the TTS cohort rather than the normal controls, suggestive of synergistic influences above the status of prior TTS. Also there is a nonsignificant difference in the rise of CFR in the 2 cohorts with a higher dobutamine dose, while the lower dobutamine dose led to a statistically significant lower CFR in the TTS cohort than the normal control cohort, which the authors attributed to a larger variation of CFR means in the normal controls with the larger dobutamine dose. It is conceivable that different CFR results are expected with the dobutamine stress test, or cold pressor test, or dipyridamole or adenosine in the convalescence phase of TTS, and the authors alluded to such possibilities [6]. However with the data at hand from this investigation one wonders whether there is a persistent decrease in CFR in patients many months after an index episode of TTS, at least when this is assessed with a dobutamine stress test and transthoracic Doppler echocardiography of LAD coronary flows. Is this due to an innate inclination (genetic and/or acquired) for MVD on exposure to catecholamines (epinephrine, norepinephrine, and dobutamine)? Is this a lingering effect of MVD which is destined to normalize after a few more months in
Letter to the Editor
patients with TTS? In reference to this, and since the dobutamine stress test was done at a mean 619 ± 297 days after the index episode of TTS [6], one wonders whether there was a relationship between CFR at low or high dobutamine dose and the time interval between the inception of the illness and the performance of the dobutamine stress test. Finally the authors of this study [6] could provide us with valuable insights if they repeat the dobutamine stress test in their patients a year from the previous test in all, or some of their 22 patients with TTS, with or without a study of the normal controls.
Conflicts of interest None.
References [1] N. Khalid, I. Iqbal, R. Coram, T. Raza, I. Fahsah, S. Ikram, Thrombolysis in myocardial infarction frame count in Takotsubo cardiomyopathy, Int. J. Cardiol. 191 (2015) 107–108. [2] P. Meimoun, D. Malaquin, S. Sayah, et al., The coronary flow reserve is transiently impaired in Tako-tsubo cardiomyopathy: a prospective study using serial Doppler transthoracic echocardiography, J. Am. Soc. Echocardiogr. 21 (2008) 72–77. [3] S. Yanagi, K. Nagae, K. Yoshida, et al., Evaluation of coronary flow reserve using Doppler guide wire in patients with ampulla cardiomyopathy: three case reports, J. Cardiol. 39 (2002) 305–312. [4] T. Kume, T. Akasaka, T. Kawamoto, et al., Assessment of coronary microcirculation in patients with Takotsubo-like left ventricular dysfunction, Circ. J. 69 (2005) 934–939.
175
[5] F. Rigo, R. Sicari, R. Citro, et al., Diffuse, marked, reversible impairment in coronary microcirculation in stress cardiomyopathy: a Doppler transthoracic echo study, Ann. Med. 41 (2009) 462–470. [6] O. Collste, P. Tornvall, M. Alam, M. Frick, Coronary flow reserve during dobutamine stress in Takotsubo stress cardiomyopathy, BMJ Open 5 (7) (Jul 16 2015) e007671. [7] S.D. Brewington, A.A. Abbas, S.R. Dixon, C.L. Grines, W.W. O'Neill, Reproducible microvascular dysfunction with dobutamine infusion in Takotsubo cardiomyopathy presenting with ST segment elevation, Catheter. Cardiovasc. Interv. 68 (2006) 769–774. [8] J. Cherian, S. Kothari, D. Angelis, A. Atef, B. Downey, J. Kirkpatrick Jr., Atypical Takotsubo cardiomyopathy: dobutamine-precipitated apical ballooning with left ventricular outflow tract obstruction, Tex. Heart Inst. J. 35 (2008) 73–75. [9] R. Margey, P. Diamond, H. McCann, D. Sugrue, Dobutamine stress echo-induced apical ballooning (Takotsubo) syndrome, Eur. J. Echocardiogr. 10 (2009) 395–399. [10] B. Uznańska, M. Plewka, K. Wierzbowska-Drabik, L. Chrzanowski, J.D. Kasprzak, Early prediction of ventricular recovery in Takotsubo syndrome using stress and contrast echocardiography, Med. Sci. Monit. 15 (2009) CS89–CS94. [11] F.J. Vasconcelos Filho, C.A. Gomes, O.A. Queiroz, J.E. Barreto, Dobutamine stress echocardiography-induced broken heart syndrome (Takotsubo syndrome), Arq. Bras. Cardiol. 93 (2009) e5–e7. [12] O. Sonmez, C. Duman, M.A. Duzenli, M. Tokac, Special attention for elderly women: atypical left ventricular apical ballooning syndrome induced by dobutamine stress test: a case report, J. Am. Geriatr. Soc. 57 (2009) 1735–1736. [13] C. Cadeddu, S. Nocco, F. Cadeddu, M., et al., Inverted Takotsubo cardiomyopathy induced by dobutamine stress echocardiography with atypical presentation, Case Rep. Cardiol. 2011 (2011) 413645. [14] A.M. Arias, P.F. Oberti, R. Pizarro, et al., Dobutamine-precipitated Takotsubo cardiomyopathy mimicking acute myocardial infarction: a multimodality image approach, Circulation 124 (2011) e312–e315. [15] J.E. Madias, Dobutamine stress echocardiography and Takotsubo syndrome: could milder forms of this pathology confound the diagnostic value of the test? Echocardiography 30 (2013) 737.