Perioperative Myocardial Injury and Infarction: Top-20 List of What We Know and What We Don’t

See Articles, p 173 and p 187 This issue of Anesthesia & Analgesia contains 2 narrative review articles that focus on the important topic of myocardial injury and infarction after noncardiac surgery. De Hert and Lurati Buse1 describe in detail how cardiac biomarkers, specifically cardiac troponin (cTn) and high-sensitivity cTn (hscTn) and brain natriuretic peptides (BNP or N-terminal probrain natriuretic peptide [NT-proBNP]), may be used to predict and detect cardiac events after noncardiac surgery. The second article by Ruetzler et al2 centers on the epidemiology and etiology of myocardial injury and infarction after noncardiac surgery and discusses preventive and therapeutic strategies. The goal of this commentary is not to duplicate topics discussed in these excellent review articles but to outline the current knowns and unknowns in this field and to provide fundamental concepts that may help the reader better interpret these articles. The commentary will focus on 3 areas: (1) cardiac biomarkers, (2) fundamental diagnostic concepts, and (3) perioperative myocardial injury and infarction. CARDIAC BIOMARKERS 1. cTn has near-absolute myocardial tissue specificity. When detected, its origin is virtually always the myocardium (in rare chronic skeletal muscle diseases, cTn T [cTnT] may become elevated). 2. cTn assays measure either cTn I (cTnI) or cTnT. There are more than 30 different cTn assays, and none of them are standardized or harmonized. Each assay has its own analytical characteristics; the most important being the 99th percentile (of the upper reference limit [URL], the 10% coefficient of variation [CV] concentration, the limit of detection [LoD]).3 3. The 99th percentile of a cTn assay distinguishes normal from pathologic. Any cTn value above the 99th percentile is abnormal and referred to as “troponin elevation.” To distinguish acute from chronic cTn elevation, 2 samples are required to detect dynamic (serial) changes such as a rise/fall pattern. 4. Severe noncardiac conditions such as end-stage renal disease (ESRD) or chronic obstructive pulmonary disease (COPD) can cause chronically elevated cTn due to associated cardiovascular comorbidities. Chronic cardiac conditions such as heart failure can cause chronically elevated cTn or acute (changing) increases with decompensation. 5. Both contemporary and high-sensitivity cTn assays measure the same molecule cTnI or cTnT; however, hscTn assays have become markedly more sensitive and detect substantially lower cTn concentrations, even in the absence of acute cardiac events. hscTn assays can detect circulating cTn values in most individuals. A cTn assay is regarded as highly sensitive when it is able to detect cTn ≥50% in both men and women (women have lower values) of a normal reference population.4 6. Increased sensitivity of hscTn assays has required a new nomenclature: hscTn values are now reported in nanogram per liter. For example, hscTnT measured at 14 ng/L would have been reported as 0.014 µg/L (or ng/mL) using a contemporary assay. The designation of nanogram per liter can be used to identify high sensitivity assays. 7. In most cardiac conditions, different cardiac biomarkers are often simultaneously elevated. For example, in heart failure, hscTn and BNP concentrations are commonly jointly elevated. 8. Not all cardiac biomarker elevations are pathologic. For example, athletes may experience elevated cTn values after strenuous exercise which may be a normal physiological response. DIAGNOSTIC CONCEPTS 9. Myocardial injury is a biochemical diagnosis identified by the detection of an abnormal cTn value. If cTn values are stable, myocardial injury is considered chronic. If cTn values show a dynamic pattern (most commonly a rising pattern), myocardial injury is considered acute. 10. Many conditions can cause myocardial injury. The cause of myocardial injury can be cardiac or extracardiac (eg, sepsis) due to effects on the heart caused by these conditions. Cardiac causes can be coronary (eg, acute coronary thrombosis) or extracoronary (eg, tachyarrhythmia). The presence of acute myocardial injury does not identify the underlying cause. 11. The corresponding myocardial tissue damage in nonischemic acute myocardial injury detected by hscTn may be small and even undetectable by cardiac imaging. The myocardial tissue damage in acute myocardial infarction (MI) is usually several orders of magnitude larger than in nonischemic acute myocardial injury. For example, an acute increase in hscTnT from 10 to 20 ng/L meets the diagnostic criteria for acute myocardial injury but does not reflect major myocardial tissue damage. Conversely, hscTn may rise to many thousands, or with some assays, hundreds of thousands nanogram per liter in an acute ST elevation MI. 12. The diagnosis of acute MI requires evidence of acute myocardial injury and evidence of acute myocardial ischemia (eg, chest pain, ischemic electrocardiogram [ECG] changes). 13. The diagnosis of acute MI should follow the guidelines set out in the Fourth Universal Definition of Myocardial Infarction (2018).5 14. Myocardial injury and MI are 2 distinct concepts and should not be used interchangeably. 15. Acute MI may develop in the absence of coronary artery disease, for instance due to prolonged myocardial ischemia. PERIOPERATIVE MYOCARDIAL INJURY AND INFARCTION 16. Currently, there is no consensus how perioperative myocardial injury and infarction should be defined. Myocardial injury after noncardiac surgery (MINS) is defined as myocardial injury thought to be due to myocardial ischemia in the absence of other overt nonischemic causes.6 Others do not include myocardial ischemia in the definition of perioperative myocardial injury to avoid confusion with the definition of acute MI. 17. The detection of new postoperative cTn elevation or myocardial injury is strongly and unequivocally associated with worse outcomes such as 30-day mortality. 18. Elevated cTn before surgery is strongly associated with increased perioperative cardiac risk. 19. There is currently no consensus whether to measure cardiac biomarkers in high-risk patients before surgery and how to manage these patients when a preoperative cardiac biomarker elevation is detected.7 20. There is currently also no consensus whether to (serially) measure cTn after surgery in high-risk patients and how to manage patients who developed elevated cardiac biomarkers after surgery. It is the hope of the author that this list of knowns and unknowns will help the reader better interpret not only the 2 review articles, but current knowledge and knowledge gaps in the important area of myocardial injury and infarction after noncardiac surgery. DISCLOSURES Name: Peter Nagele, MD, MSc. Contribution: This author is the sole author. Conflicts of Interest: In the past 24 months, P. Nagele has received research funding from National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI), NIH/National Institute of General Medical Sciences (NIGMS), NIH/National Institute of Mental Health (NIMH), American Foundation for the Prevention of Suicide, the Brain and Behavior Foundation/National Alliance for Research on Schizophrenia & Depression (NARSAD), Roche Diagnostics and Abbott Diagnostics and has served on an advisory board for Roche Diagnostics. This manuscript was handled by: Richard C. Prielipp, MD, MBA.