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Postconditioning or preconditioning, which should be promoted for protecting from ischemic reperfusion injury? Response to letter IJC-D-14-02875
International Journal of Cardiology 176 (2014) 1383–1384
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Postconditioning or preconditioning, which should be promoted for protecting from ischemic reperfusion injury? Response to letter IJC-D-14-02875☆ Vicente Bodi a,⁎, Clara Bonanad a, Juan M. Ruiz-Nodar b a b
Cardiology Department, Hospital Clinico Universitario-INCLIVA, University of Valencia, Valencia, Spain Cardiology Department, Hospital General Universitario, Alicante, Spain
a r t i c l e
i n f o
Article history: Received 31 July 2014 Accepted 2 August 2014 Available online 10 August 2014 Keywords: Myocardial infarction Perfusion Ischemic postconditioning
We are deeply grateful to Dr. Zhong and colleagues for their interest in our paper recently published in the International Journal of Cardiology entitled “Effect of ischemic postconditioning on microvascular obstruction in reperfused myocardial infarction. Results of a randomized study in patients and of an experimental model in swine” [1]. We agree with Dr. Zhong and colleagues [2] regarding the fact that it cannot be completely discarded yet that ischemic postconditioning (PCON) could exert a beneficial effect in a very specific subset of patients. Unfortunately, the fact is that after a number of preliminary studies showing promising results in short series of patients and using surrogates of infarct size, recent data are either controversial or disappointing. The largest study focused on the effect of PCON on reperfusion after ST-segment elevation myocardial infarction (STEMI), the POST trial [3], failed to demonstrate a benefit in terms of ST-segment resolution associated with this therapy. Cardiovascular magnetic resonance (CMR) has become the gold standard noninvasive imaging technique for a comprehensive evaluation of the structural consequences of STEMI [4]. Using this technique the most recent studies suggest that PCON does not contribute to reduce myocardial and microvascular damages when compared with primary angioplasty alone [1,5–7]. We share with Dr. Zhong and colleagues their thought that PCON is not an
☆ Competing interests: No competing interests exist in the present study. ⁎ Corresponding author at: Cardiology Department, Hospital Clinico UniversitarioINCLIVA, University of Valencia, Blasco Ibanez 17, 46010 Valencia, Spain. Tel./fax: +34 96 3862658. E-mail address: [email protected] (V. Bodi).
http://dx.doi.org/10.1016/j.ijcard.2014.08.028 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
innocuous technique and, as already suggested [5,6], it could potentially bring about deleterious consequences. Before a widespread use of this option, a clear benefit in terms of myocardial and microvascular damage attenuations and, especially, in terms of patients' outcome should be consistently demonstrated. However, the structural benefit of PCON is unclear and its clinical efficacy is unknown. We encourage Dr. Zhong and colleagues to carry out a meta-analysis of published data. Dr. Zhong and colleagues point out the limitations of creatine kinase MB for detecting myocardial ischemia and injury. We agree with them, that is the reason why this biomarker was not taken into consideration at all in our study for assessing the extent of damage on the left ventricle. For this purpose, as it is currently accepted [4], the ideal technique is CMR. We share with Dr. Zhong and colleagues their interest for new biomarkers, beyond troponins, to more timely and accurately identify myocardial ischemia and injury in the wide spectrum of ischemic heart disease [8]. We are not sure, however, that analyzing the effects of PCON in STEMI patients is the best scenario for new biomarkers such as ischemia modified albumin. Beyond the pathophysiological interest, severe myocardial ischemia universally occurs in STEMI; consequently, new and highly sensitive ischemia biomarkers always rise in this context [7]. As mentioned above, the translation of new therapeutic options to routine clinical practice needs consistent validation by the state-of-the-art imaging technique (CMR) and by monitoring the effect on patients' outcome. We encourage Dr. Zhong and colleagues on their endeavor to demonstrate the usefulness of remote conditioning. Though its benefit has not been definitively established [9], this is a harmless and inexpensive strategy. Regarding PCON, on the basis of the available evidence, its routine use in the revascularization of STEMI patients cannot be recommended. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. Acknowledgments and funding The present study was supported by the “Instituto de Salud Carlos III” (PI1102323 grant), FEDER, the “Conselleria de Educacio, Cultura i
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V. Bodi et al. / International Journal of Cardiology 176 (2014) 1383–1384
Esport de la Generalitat Valenciana” (PROMETEO/2013/007 grant) and by the Regensburger Forschungsförderung in der Medizin (ReForM). References [1] Bodi V, Ruiz-Nodar JM, Feliu E, et al. Effect of ischemic postconditioning on microvascular obstruction in reperfused myocardial infarction. Results of a randomized study in patients and of an experimental model in swine. Int J Cardiol 2014;175:138–46. [2] Zhong Y, Wang N. Postconditioning or preconditioning, which should be promoted in the protecting of ischemic reperfusion injury? Int J Cardiol; 2014. IJC-D-14–02875. [3] Hahn JY, Song YB, Kim EK, et al. Ischemic postconditioning during primary percutaneous coronary intervention: the effects of postconditioning on myocardial reperfusion in patients with st-segment elevation myocardial infarction (post) randomized trial. Circulation 2013;128:1889–96. [4] Dall'Armellina E, Karamitsos TD, Neubauer S, Choudhury RP. CMR for characterization of the myocardium in acute coronary syndromes. Nat Rev Cardiol 2010;7:624–36.
[5] Freixa X, Bellera N, Ortiz-Pérez JT, et al. Ischaemic postconditioning revisited: lack of effects on infarct size following primary percutaneous coronary intervention. Eur Heart J 2012;33:103–12. [6] Tarantini G, Favaretto E, Marra MP, et al. Postconditioning during coronary angioplasty in acute myocardial infarction: the POST-AMI trial. Int J Cardiol 2012;162:33–8. [7] Roubille F, Mewton N, Elbaz M, et al. No post-conditioning in the human heart with thrombolysis in myocardial infarction flow 2–3 on admission. Eur Heart J 2014;35: 1675–82. [8] Bodi V, Sanchis J, Morales JM, et al. Metabolomic profile of human myocardial ischemia by nuclear magnetic resonance spectroscopy of peripheral blood serum. A translational study based on transient coronary occlusion models. J Am Coll Cardiol 2012; 59:1629–41. [9] Carrasco F, Muñoz A, Dominguez A, et al. Remote ischaemic postconditioning: does it protect against ischaemic damage in percutaneous coronary revascularisation? Randomised placebo-controlled clinical trial. Heart Oct 2013;99(19):1431–7.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Postconditioning or preconditioning, which should be promoted for protecting from ischemic reperfusion injury? Response to letter IJC-D-14-02875☆ Vicente Bodi a,⁎, Clara Bonanad a, Juan M. Ruiz-Nodar b a b
Cardiology Department, Hospital Clinico Universitario-INCLIVA, University of Valencia, Valencia, Spain Cardiology Department, Hospital General Universitario, Alicante, Spain
a r t i c l e
i n f o
Article history: Received 31 July 2014 Accepted 2 August 2014 Available online 10 August 2014 Keywords: Myocardial infarction Perfusion Ischemic postconditioning
We are deeply grateful to Dr. Zhong and colleagues for their interest in our paper recently published in the International Journal of Cardiology entitled “Effect of ischemic postconditioning on microvascular obstruction in reperfused myocardial infarction. Results of a randomized study in patients and of an experimental model in swine” [1]. We agree with Dr. Zhong and colleagues [2] regarding the fact that it cannot be completely discarded yet that ischemic postconditioning (PCON) could exert a beneficial effect in a very specific subset of patients. Unfortunately, the fact is that after a number of preliminary studies showing promising results in short series of patients and using surrogates of infarct size, recent data are either controversial or disappointing. The largest study focused on the effect of PCON on reperfusion after ST-segment elevation myocardial infarction (STEMI), the POST trial [3], failed to demonstrate a benefit in terms of ST-segment resolution associated with this therapy. Cardiovascular magnetic resonance (CMR) has become the gold standard noninvasive imaging technique for a comprehensive evaluation of the structural consequences of STEMI [4]. Using this technique the most recent studies suggest that PCON does not contribute to reduce myocardial and microvascular damages when compared with primary angioplasty alone [1,5–7]. We share with Dr. Zhong and colleagues their thought that PCON is not an
☆ Competing interests: No competing interests exist in the present study. ⁎ Corresponding author at: Cardiology Department, Hospital Clinico UniversitarioINCLIVA, University of Valencia, Blasco Ibanez 17, 46010 Valencia, Spain. Tel./fax: +34 96 3862658. E-mail address: [email protected] (V. Bodi).
http://dx.doi.org/10.1016/j.ijcard.2014.08.028 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
innocuous technique and, as already suggested [5,6], it could potentially bring about deleterious consequences. Before a widespread use of this option, a clear benefit in terms of myocardial and microvascular damage attenuations and, especially, in terms of patients' outcome should be consistently demonstrated. However, the structural benefit of PCON is unclear and its clinical efficacy is unknown. We encourage Dr. Zhong and colleagues to carry out a meta-analysis of published data. Dr. Zhong and colleagues point out the limitations of creatine kinase MB for detecting myocardial ischemia and injury. We agree with them, that is the reason why this biomarker was not taken into consideration at all in our study for assessing the extent of damage on the left ventricle. For this purpose, as it is currently accepted [4], the ideal technique is CMR. We share with Dr. Zhong and colleagues their interest for new biomarkers, beyond troponins, to more timely and accurately identify myocardial ischemia and injury in the wide spectrum of ischemic heart disease [8]. We are not sure, however, that analyzing the effects of PCON in STEMI patients is the best scenario for new biomarkers such as ischemia modified albumin. Beyond the pathophysiological interest, severe myocardial ischemia universally occurs in STEMI; consequently, new and highly sensitive ischemia biomarkers always rise in this context [7]. As mentioned above, the translation of new therapeutic options to routine clinical practice needs consistent validation by the state-of-the-art imaging technique (CMR) and by monitoring the effect on patients' outcome. We encourage Dr. Zhong and colleagues on their endeavor to demonstrate the usefulness of remote conditioning. Though its benefit has not been definitively established [9], this is a harmless and inexpensive strategy. Regarding PCON, on the basis of the available evidence, its routine use in the revascularization of STEMI patients cannot be recommended. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. Acknowledgments and funding The present study was supported by the “Instituto de Salud Carlos III” (PI1102323 grant), FEDER, the “Conselleria de Educacio, Cultura i
1384
V. Bodi et al. / International Journal of Cardiology 176 (2014) 1383–1384
Esport de la Generalitat Valenciana” (PROMETEO/2013/007 grant) and by the Regensburger Forschungsförderung in der Medizin (ReForM). References [1] Bodi V, Ruiz-Nodar JM, Feliu E, et al. Effect of ischemic postconditioning on microvascular obstruction in reperfused myocardial infarction. Results of a randomized study in patients and of an experimental model in swine. Int J Cardiol 2014;175:138–46. [2] Zhong Y, Wang N. Postconditioning or preconditioning, which should be promoted in the protecting of ischemic reperfusion injury? Int J Cardiol; 2014. IJC-D-14–02875. [3] Hahn JY, Song YB, Kim EK, et al. Ischemic postconditioning during primary percutaneous coronary intervention: the effects of postconditioning on myocardial reperfusion in patients with st-segment elevation myocardial infarction (post) randomized trial. Circulation 2013;128:1889–96. [4] Dall'Armellina E, Karamitsos TD, Neubauer S, Choudhury RP. CMR for characterization of the myocardium in acute coronary syndromes. Nat Rev Cardiol 2010;7:624–36.
[5] Freixa X, Bellera N, Ortiz-Pérez JT, et al. Ischaemic postconditioning revisited: lack of effects on infarct size following primary percutaneous coronary intervention. Eur Heart J 2012;33:103–12. [6] Tarantini G, Favaretto E, Marra MP, et al. Postconditioning during coronary angioplasty in acute myocardial infarction: the POST-AMI trial. Int J Cardiol 2012;162:33–8. [7] Roubille F, Mewton N, Elbaz M, et al. No post-conditioning in the human heart with thrombolysis in myocardial infarction flow 2–3 on admission. Eur Heart J 2014;35: 1675–82. [8] Bodi V, Sanchis J, Morales JM, et al. Metabolomic profile of human myocardial ischemia by nuclear magnetic resonance spectroscopy of peripheral blood serum. A translational study based on transient coronary occlusion models. J Am Coll Cardiol 2012; 59:1629–41. [9] Carrasco F, Muñoz A, Dominguez A, et al. Remote ischaemic postconditioning: does it protect against ischaemic damage in percutaneous coronary revascularisation? Randomised placebo-controlled clinical trial. Heart Oct 2013;99(19):1431–7.