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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Jun 26, 2020; 12(6): 231-247
Published online Jun 26, 2020. doi: 10.4330/wjc.v12.i6.231
Autonomic neurocardiogenic syndrome is stonewalled by the universal definition of myocardial infarction
Shams Y-Hassan
Shams Y-Hassan, Coronary Artery Disease Area, Heart and Vascular Theme, Karolinska Institutet and Karolinska University Hospital, Stockholm S-141 86, Sweden
Author contributions: Y-Hassan S designed, edited, and wrote the paper.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Shams Y-Hassan, MBChB, MD, Doctor, Research Scientist, Cardiologist senior consultant, Coronary Artery Disease Area, Heart and Vascular Theme, Karolinska Institutet and Karolinska University Hospital, SE‐171 76, Stockholm S-141 86, Stockholm, Sweden. shams.younis-hassan@sll.se
Received: October 30, 2019
Peer-review started: October 30, 2019
First decision: December 12, 2019
Revised: April 27, 2020
Accepted: May 14, 2020
Article in press: May 14, 2020
Published online: June 26, 2020
Processing time: 240 Days and 5.5 Hours
Abstract

Myocardial infarction (MI) is defined as myocardial cell death due to prolonged myocardial ischemia. Clinically, troponin rise and/or fall have become the “defining feature of MI” according to the universal definition of MI (UD-MI). Takotsubo syndrome (TS) and TS-related disease conditions also cause troponin elevation with typical rise and/or fall pattern but through a mechanism other than coronary ischemia. By strict application of the clinical diagnostic criteria for type-1 MI, type-2 MI, type-3 MI, and MI with non-obstructive coronary arteries according to the UD-MI including the fourth one published recently, TS and most of the 26 other causes of troponin elevation mentioned in the fourth UD-MI may erroneously be classified as MI. The existing evidence argues for the case that TS by itself is not a MI. Hyper-activation of the autonomic-sympathetic nervous system including local cardiac sympathetic hyper-activation and disruption with nor-epinephrine churn and spillover is the most probable cause of TS. This autonomic neuro-cardiogenic (ANCA) mechanism results in myocardial “cramp” (stunning), the severity and duration of which depend on the degree of the sympathetic-hyperactivation and nor-epinephrine spillover. The myocardial cramp may squeeze the cytosolic free troponin pools causing mild to moderate troponin elevation in TS and TS-related disease conditions. This ANCA syndrome, which has hitherto been enveloped by the UD-MI over more than one decade, may occur in acute, recurrent, and chronic forms. In this critical review, the controversies of UD-MI, evidence for ANCA syndrome, and a hypothetical mechanism for the troponin elevation in ANCA syndrome are provided.

Keywords: Universal definition; Myocardial infarction; Takotsubo; Myocardial stunning; Cardiac cramp; Autonomic neurocardiogenic syndrome; Heart failure; Chronic kidney diseases

Core tip: The fourth universal definition of myocardial infarction (MI) needs reconsideration. Type 2 MI and MI with non-obstructive coronary arteries are not evidence-based. Autonomic neuro-cardiogenic (ANCA) syndrome is the second important cause of troponin elevation after acute coronary ischemia. Troponin release in ANCA syndrome is most probably due to cardiac cramp squeezing the cardiomyocyte causing mild to moderate release of troponin from the cytosolic free pool. ANCA syndrome may occur in an acute form as in takotsubo syndrome. The syndrome may also occur in recurrent or a chronic form as in chronic heart failure with acute exacerbations, and chronic kidney diseases.