RESPONSE TO LETTER TO THE EDITOR
Response by Lindahl et al to Letter Regarding Article, “Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease” Downloaded from http://circ.ahajournals.org/ by guest on September 13, 2017
In Response: We appreciate the valuable comments by Ciliberti et al in their letter to the editor on our article on medical therapy in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA).1 Ciliberti et al raise several important issues on which we are happy to further comment. Our study population consisted of 9136 consecutive patients with acute myocardial infarction (AMI) and without any significant obstruction (≥50%) on coronary angiography reported to the nationwide quality registry, SWEDEHEART, during a 10-year period. We agree that there is a heterogeneity in this real-life population in terms of the underlying mechanisms for MINOCA. There is certainly a significant group of patients given the clinical diagnosis of MINOCA who would have been diagnosed with myocarditis if systematically examined by cardiac magnetic resonance.2 However, how much of the MINOCA population actually has myocarditis is dependent on how strictly the criteria of the AMI diagnosis are applied. Although 33% were found to have myocarditis on cardiac magnetic resonance in a metaanalysis, the prevalence varied between 7% and 63% in the 5 included studies.2 Nevertheless, as suggested by Ciliberti et al, the inclusion of myocarditis may have affected the results of our study, most probably diluting the effects of the examined treatments. The question of Takotsubo cardiomyopathy (TTC), however, is much more complicated. Patients fulfilling the diagnostic criteria of TTC3 should not be given the diagnosis of AMI according to the universal definition of myocardial infarction, which also is stressed in the instructions for the SWEDEHEART registry. However, TTC was not a well-known entity in the first part of the study period of 2003 to 2013; hence, a number of TTC patients fulfilling the diagnostic criteria of TTC were most certainly given an AMI diagnosis and thus included in the study population, as pointed out by Ciliberti et al and discussed in the Limitations section. Furthermore, the boundary between TTC and MINOCA is far from clear. As suggested, there are probably “mild” forms of TTC, not fulfilling the more stringent clinical criteria, that would be identified if early cardiac magnetic resonance examinations were done systematically.4 This has led the authors of a recent position paper on MINOCA to suggest that TTC should be included in the MINOCA syndrome.5 We slightly disagree with Ciliberti et al about the treatment of TTC; although position documents are published,3 there is a lack of randomized clinical trials evaluating treatment in TTC. We also agree with Ciliberti et al that future studies should analyze separately patients with mildly atherosclerotic coronary arteries and those without any evidence of atherosclerosis. This would ideally be performed with other, more sensitive techniques than coronary angiography. Unfortunately, the observational nature of our study precludes us from drawing any conclusions about the mechanisms of the beneficial effect of the treatments studied. This would of course be 1082
September 12, 2017
Bertil Lindahl, MD, PhD Tomasz Baron, MD, PhD David Erlinge, MD, PhD Nermin Hadziosmanovic, MSc Anna Nordenskjöld, MD, PhD Anton Gard, MD Tomas Jernberg, MD, PhD
Circulation is available at http://circ.ahajournals.org. © 2017 American Heart Association, Inc.
Circulation. 2017;136:1082–1083. DOI: 10.1161/CIRCULATIONAHA.117.029938
Response to Letter to the Editor
DISCLOSURES Dr Jernberg received lecture and consultancy/advisory board fees from AstraZeneca, Aspen, Amgen, and MSD. The other authors report no conflicts.
AFFILIATIONS Downloaded from http://circ.ahajournals.org/ by guest on September 13, 2017
From Department of Medical Sciences, Cardiology (B.L., T.B., A.G.) and Uppsala Clinical Research Center, Uppsala University, Sweden (B.L., T.B., N.H., A.G.); Department of Cardiology, Lund University, Sweden (D.E.); Department of Cardiology, Faculty of Health, Örebro University, Sweden (A.N.); and Department of Clinical Sciences, Cardiology, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden (T.J.).
Circulation. 2017;136:1082–1083. DOI: 10.1161/CIRCULATIONAHA.117.029938
REFERENCES 1. Lindahl B, Baron T, Erlinge D, Hadziosmanovic N, Nordenskjöld A, Gard A, Jernberg T. Medical therapy for secondary prevention and long-term outcome in patients with myocardial infarction with nonobstructive coronary artery disease. Circulation. 2017;135:1481–1489. doi: 10.1161/CIRCULATIONAHA.116.026336. 2. Tornvall P, Gerbaud E, Behaghel A, Chopard R, Collste O, Laraudogoitia E, Leurent G, Meneveau N, Montaudon M, Perez-David E, Sörensson P, Agewall S. Myocarditis or “true” infarction by cardiac magnetic resonance in patients with a clinical diagnosis of myocardial infarction without obstructive coronary disease: A meta-analysis of individual patient data. Atherosclerosis. 2015;241:87–91. doi: 10.1016/j.atherosclerosis.2015.04.816. 3. Lyon AR, Bossone E, Schneider B, Sechtem U, Citro R, Underwood SR, Sheppard MN, Figtree GA, Parodi G, Akashi YJ, Ruschitzka F, Filippatos G, Mebazaa A, Omerovic E. Current state of knowledge on Takotsubo syndrome: a position statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2016;18:8–27. doi: 10.1002/ejhf.424. 4. Plácido R, Cunha Lopes B, Almeida AG, Rochitte CE. The role of cardiovascular magnetic resonance in takotsubo syndrome. J Cardiovasc Magn Reson. 2016;18:68. doi: 10.1186/s12968-016-0279-5. 5. Agewall S, Beltrame JF, Reynolds HR, Niessner A, Rosano G, Caforio AL, De Caterina R, Zimarino M, Roffi M, Kjeldsen K, Atar D, Kaski JC, Sechtem U, Tornvall P; Working Group on Cardiovascular Pharmacotherapy. ESC Working Group position paper on myocardial infarction with non-obstructive coronary arteries. Eur Heart J. 2017;38:143–153. doi: 10.1093/ eurheartj/ehw149.
September 12, 2017
1083
CORRESPONDENCE
very important to study further in properly designed mechanistic studies. Finally, we fully support the notion of the need for a “universal definition of MINOCA,” especially because MINOCA does not fit with the current classification of AMI in types 1 through 5.
Response by Lindahl et al to Letter Regarding Article, ''Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease'' Bertil Lindahl, Tomasz Baron, David Erlinge, Nermin Hadziosmanovic, Anna Nordenskjöld, Anton Gard and Tomas Jernberg Downloaded from http://circ.ahajournals.org/ by guest on September 13, 2017
Circulation. 2017;136:1082-1083 doi: 10.1161/CIRCULATIONAHA.117.029938 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2017 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/136/11/1082
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/
Response by Lindahl et al to Letter Regarding Article, “Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease” Downloaded from http://circ.ahajournals.org/ by guest on September 13, 2017
In Response: We appreciate the valuable comments by Ciliberti et al in their letter to the editor on our article on medical therapy in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA).1 Ciliberti et al raise several important issues on which we are happy to further comment. Our study population consisted of 9136 consecutive patients with acute myocardial infarction (AMI) and without any significant obstruction (≥50%) on coronary angiography reported to the nationwide quality registry, SWEDEHEART, during a 10-year period. We agree that there is a heterogeneity in this real-life population in terms of the underlying mechanisms for MINOCA. There is certainly a significant group of patients given the clinical diagnosis of MINOCA who would have been diagnosed with myocarditis if systematically examined by cardiac magnetic resonance.2 However, how much of the MINOCA population actually has myocarditis is dependent on how strictly the criteria of the AMI diagnosis are applied. Although 33% were found to have myocarditis on cardiac magnetic resonance in a metaanalysis, the prevalence varied between 7% and 63% in the 5 included studies.2 Nevertheless, as suggested by Ciliberti et al, the inclusion of myocarditis may have affected the results of our study, most probably diluting the effects of the examined treatments. The question of Takotsubo cardiomyopathy (TTC), however, is much more complicated. Patients fulfilling the diagnostic criteria of TTC3 should not be given the diagnosis of AMI according to the universal definition of myocardial infarction, which also is stressed in the instructions for the SWEDEHEART registry. However, TTC was not a well-known entity in the first part of the study period of 2003 to 2013; hence, a number of TTC patients fulfilling the diagnostic criteria of TTC were most certainly given an AMI diagnosis and thus included in the study population, as pointed out by Ciliberti et al and discussed in the Limitations section. Furthermore, the boundary between TTC and MINOCA is far from clear. As suggested, there are probably “mild” forms of TTC, not fulfilling the more stringent clinical criteria, that would be identified if early cardiac magnetic resonance examinations were done systematically.4 This has led the authors of a recent position paper on MINOCA to suggest that TTC should be included in the MINOCA syndrome.5 We slightly disagree with Ciliberti et al about the treatment of TTC; although position documents are published,3 there is a lack of randomized clinical trials evaluating treatment in TTC. We also agree with Ciliberti et al that future studies should analyze separately patients with mildly atherosclerotic coronary arteries and those without any evidence of atherosclerosis. This would ideally be performed with other, more sensitive techniques than coronary angiography. Unfortunately, the observational nature of our study precludes us from drawing any conclusions about the mechanisms of the beneficial effect of the treatments studied. This would of course be 1082
September 12, 2017
Bertil Lindahl, MD, PhD Tomasz Baron, MD, PhD David Erlinge, MD, PhD Nermin Hadziosmanovic, MSc Anna Nordenskjöld, MD, PhD Anton Gard, MD Tomas Jernberg, MD, PhD
Circulation is available at http://circ.ahajournals.org. © 2017 American Heart Association, Inc.
Circulation. 2017;136:1082–1083. DOI: 10.1161/CIRCULATIONAHA.117.029938
Response to Letter to the Editor
DISCLOSURES Dr Jernberg received lecture and consultancy/advisory board fees from AstraZeneca, Aspen, Amgen, and MSD. The other authors report no conflicts.
AFFILIATIONS Downloaded from http://circ.ahajournals.org/ by guest on September 13, 2017
From Department of Medical Sciences, Cardiology (B.L., T.B., A.G.) and Uppsala Clinical Research Center, Uppsala University, Sweden (B.L., T.B., N.H., A.G.); Department of Cardiology, Lund University, Sweden (D.E.); Department of Cardiology, Faculty of Health, Örebro University, Sweden (A.N.); and Department of Clinical Sciences, Cardiology, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden (T.J.).
Circulation. 2017;136:1082–1083. DOI: 10.1161/CIRCULATIONAHA.117.029938
REFERENCES 1. Lindahl B, Baron T, Erlinge D, Hadziosmanovic N, Nordenskjöld A, Gard A, Jernberg T. Medical therapy for secondary prevention and long-term outcome in patients with myocardial infarction with nonobstructive coronary artery disease. Circulation. 2017;135:1481–1489. doi: 10.1161/CIRCULATIONAHA.116.026336. 2. Tornvall P, Gerbaud E, Behaghel A, Chopard R, Collste O, Laraudogoitia E, Leurent G, Meneveau N, Montaudon M, Perez-David E, Sörensson P, Agewall S. Myocarditis or “true” infarction by cardiac magnetic resonance in patients with a clinical diagnosis of myocardial infarction without obstructive coronary disease: A meta-analysis of individual patient data. Atherosclerosis. 2015;241:87–91. doi: 10.1016/j.atherosclerosis.2015.04.816. 3. Lyon AR, Bossone E, Schneider B, Sechtem U, Citro R, Underwood SR, Sheppard MN, Figtree GA, Parodi G, Akashi YJ, Ruschitzka F, Filippatos G, Mebazaa A, Omerovic E. Current state of knowledge on Takotsubo syndrome: a position statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2016;18:8–27. doi: 10.1002/ejhf.424. 4. Plácido R, Cunha Lopes B, Almeida AG, Rochitte CE. The role of cardiovascular magnetic resonance in takotsubo syndrome. J Cardiovasc Magn Reson. 2016;18:68. doi: 10.1186/s12968-016-0279-5. 5. Agewall S, Beltrame JF, Reynolds HR, Niessner A, Rosano G, Caforio AL, De Caterina R, Zimarino M, Roffi M, Kjeldsen K, Atar D, Kaski JC, Sechtem U, Tornvall P; Working Group on Cardiovascular Pharmacotherapy. ESC Working Group position paper on myocardial infarction with non-obstructive coronary arteries. Eur Heart J. 2017;38:143–153. doi: 10.1093/ eurheartj/ehw149.
September 12, 2017
1083
CORRESPONDENCE
very important to study further in properly designed mechanistic studies. Finally, we fully support the notion of the need for a “universal definition of MINOCA,” especially because MINOCA does not fit with the current classification of AMI in types 1 through 5.
Response by Lindahl et al to Letter Regarding Article, ''Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease'' Bertil Lindahl, Tomasz Baron, David Erlinge, Nermin Hadziosmanovic, Anna Nordenskjöld, Anton Gard and Tomas Jernberg Downloaded from http://circ.ahajournals.org/ by guest on September 13, 2017
Circulation. 2017;136:1082-1083 doi: 10.1161/CIRCULATIONAHA.117.029938 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2017 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/136/11/1082
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/
