Assessment and Treatment of Patients With Type 2 Myocardial Infarction and Acute Nonischemic Myocardial Injury

Although coronary thrombus overlying a disrupted atherosclerotic plaque has long been considered the hallmark and the primary therapeutic target for acute myocardial infarction (MI), multiple other mechanisms are now known to cause or contribute to MI. It is further recognized that an MI is just one of many types of acute myocardial injury. The Fourth Universal Definition of Myocardial Infarction provides a taxonomy for acute myocardial injury, including 5 subtypes of MI and nonischemic myocardial injury. The diagnosis of MI is reserved for patients with myocardial ischemia as the cause of myocardial injury, whether attributable to acute atherothrombosis (type 1 MI) or supply/demand mismatch without acute atherothrombosis (type 2 MI). Myocardial injury in the absence of ischemia is categorized as acute or chronic nonischemic myocardial injury. However, optimal evaluation and treatment strategies for these etiologically distinct diagnoses have yet to be defined. Herein, we review the epidemiology, risk factor associations, and diagnostic tools that may assist in differentiating between nonischemic myocardial injury, type 1 MI, and type 2 MI. We identify limitations, review new research, and propose a framework for the diagnostic and therapeutic approach for patients who have suspected MI or other causes of myocardial injury.

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249High-sensitivity cardiac troponin and the universal definition of myocardial infarction: a randomised controlled trial

European Heart Journal ◽

10.1093/eurheartj/ehz747.0066 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

A R Chapman ◽

P D Adamson ◽

A Anand ◽

A S V Shah ◽

K K Lee ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Troponin ◽

Myocardial Injury ◽

Primary Outcome ◽

Controlled Trial ◽

High Sensitivity ◽

Cardiovascular Death ◽

Acute Myocardial Injury ◽

Universal Definition

Abstract Background The Universal Definition of Myocardial Infarction recommends the 99th centile diagnostic threshold using a high-sensitivity cardiac troponin (hs-cTn) assay and the classification of patients by the etiology of myocardial injury. Whether implementation of this definition improves risk stratification, treatment or outcomes is unknown. Methods In a stepped-wedge cluster randomized controlled trial, we implemented a high-sensitivity troponin assay and the recommendations of the Universal Definition in 48,282 consecutive patients with suspected acute coronary syndrome across ten hospitals. In a pre-specified secondary analysis, we compared the primary outcome of myocardial infarction or cardiovascular death, and secondary outcome of non-cardiovascular death at one year across diagnostic categories as per the Fourth Universal Definition. We applied competing risks methodology in all analyses, using a cumulative incidence function and determining the cause-specific hazard ratio (csHR) for competing outcomes. Results Cardiac troponin concentrations were elevated in 21.5% (10,360/48,282) of all trial participants. Implementation increased the diagnosis of type 1 myocardial infarction by 11% (510/4,471), type 2 myocardial infarction by 22% (205/916), acute myocardial injury by 36% (443/1,233) and chronic myocardial injury by 43% (389/898). The risk and rate of the primary outcome was highest in those with type 1 myocardial infarction, whereas the risk and rate of non-cardiovascular death was highest in those with acute myocardial injury (Table, Figure). Despite increases in anti-platelet therapy and coronary revascularization after implementation, the primary outcome was unchanged in patients with type 1 myocardial infarction (csHR 1.00, 95% CI 0.82 to 1.21), or in any other category. Adjusted csHR for competing outcomes Myocardial infarction or cardiovascular death Non-cardiovascular death Adjusted csHR (95% CI) Adjusted csHR (95% CI) Type 1 myocardial infarction 5.64 (5.12 to 6.22) 0.83 (0.72 to 0.96) Type 2 myocardial infarction 3.50 (2.94 to 4.15) 1.72 (1.44 to 2.06) Acute myocardial injury 4.38 (3.80 to 5.05) 2.65 (2.33 to 3.00) Chronic myocardial injury 3.88 (3.31 to 4.55) 2.06 (1.77 to 2.40) Cox regression models adjusted for age, sex, diabetes, ischaemic heart disease, season, days since trial onset and site of recruitment (as a random effect). Cumulative incidence and number at risk Conclusions Implementation of the recommendations of the Universal Definition identified patients with different risks of future cardiovascular and non-cardiovascular events, but did not improve outcomes. Greater understanding of the underlying mechanisms and effective strategies for the investigation and treatment of patients with myocardial injury and infarction are required if we are to improve outcomes. Acknowledgement/Funding British Heart Foundation

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Interphysician agreement on subclassification of myocardial infarction

Heart ◽

10.1136/heartjnl-2017-312409 ◽

2018 ◽

Vol 104 (15) ◽

pp. 1284-1291 ◽

Cited By ~ 14

Author(s):

Anton Gard ◽

Bertil Lindahl ◽

Gorav Batra ◽

Nermin Hadziosmanovic ◽

Marcus Hjort ◽

...

Keyword(s):

Myocardial Infarction ◽

Myocardial Injury ◽

Interobserver Agreement ◽

Plaque Rupture ◽

Protein Levels ◽

The Third ◽

Universal Definition ◽

Definition Of

ObjectiveThe universal definition of myocardial infarction (MI) differentiates MI due to oxygen supply/demand mismatch (type 2) from MI due to plaque rupture (type 1) as well as from myocardial injuries of non-ischaemic or multifactorial nature. The purpose of this study was to investigate how often physicians agree in this classification and what factors lead to agreement or disagreement.MethodsA total of 1328 patients diagnosed with MI at eight different Swedish hospitals 2011 were included. All patients were retrospectively reclassified into different MI or myocardial injury subtypes by two independent specially trained physicians, strictly adhering to the third universal definition of MI.ResultsOverall, there was a moderate interobserver agreement with a kappa coefficient (κ) of 0.55 in this classification. There was substantial agreement when distinguishing type 1 MI (κ: 0.61), compared with moderate agreement when distinguishing type 2 MI (κ: 0.54). In multivariate logistic regression analyses, ST elevation MI (P<0.001), performed coronary angiography (P<0.001) and larger changes in troponin levels (P=0.023) independently made the physicians agree significantly more often, while they disagreed more often with symptoms of dyspnoea (P<0.001), higher systolic blood pressure (P=0.001) and higher C reactive protein levels on admission (P=0.016).ConclusionDistinguishing MI types is challenging also for trained adjudicators. Although strictly adhering to the third universal definition of MI, differentiation between type 1 MI, type 2 MI and myocardial injury only gave a moderate rate of interobserver agreement. More precise and clinically applicable criteria for the current classification, particularly for type 2 MI diagnosis, are urgently needed.

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Abstract 13297: Short-Term Mortality in Patients With Myocardial Injury and Myocardial Infarction Type 1 and Type 2

Circulation ◽

10.1161/circ.132.suppl_3.13297 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Laura Sarkisian ◽

Lotte Saaby ◽

Tina S Poulsen ◽

Oke Gerke ◽

Axel C Diederichsen ◽

...

Keyword(s):

Myocardial Infarction ◽

Myocardial Injury ◽

Troponin I ◽

Clinical Indication ◽

Short Term ◽

Cox Regression Analysis ◽

Short Term Mortality

Introduction: Troponin elevations occur in a myriad of clinical conditions other than myocardial infarction (MI) and imply a poor prognosis. So far, data comparing the short-term outcome in patients with myocardial injury vs. patients with type 1 or type 2 MI are not available. Methods: Over a 1-year period we prospectively studied hospitalized patients having cardiac troponin I (cTnI) measured on clinical indication. The diagnosis of type 1 and type 2 MI was according to the universal definition involving a rising and/or falling pattern of cTnI values above the decision limit of 30 ng/L. cTnI elevations above this limit in patients without overt myocardial ischemia were defined as myocardial injury. A 1-month follow-up was done with mortality as endpoint. Results: The study covered 1577 consecutive patients with cTnI values >30 ng/L, of whom 360 had a type 1 MI, 119 a type 2 MI and 1089 had myocardial injury. Type 1 MI patients were younger with a median age of 70 (IQR 61-81) yrs, whereas the median ages in type 2 MI and myocardial injury were higher but comparable : 78 (IQR 67-84) vs. 77 (IQR 67-85) yrs. Peak cTnI values, however, were highest in type 1 MI: 3820 (530-19030) ng/L, lower in type 2 MI: 850 (390-3270) ng/L, and smallest in patients with myocardial injury: 90 (50-270) ng/L (p=0.0001). At one-month follow-up 285 patients had died. Mortality in the different subgroups was: 9% (33/360) in type 1 MI, 24% (28/119) in type 2 MI, and 21% (224/1089) in patients with myocardial injury. The results are depicted in the figure (Kaplan-Meier curves, log-rank-test; p-value <0.0001). Multivariate COX regression analysis revealed a Hazard Ratio (95%) of 2.1 (1.2-3.7) for type 2 MI and 1.4 (0.9-2.1) for myocardial injury. Conclusion: The short-term mortality in patients with myocardial injury and type 2 MI is almost identical but higher than in patients with type 1 MI. These prognostic findings imply that the clinical distinction between myocardial injury and type 2 MI may be somewhat artificial.

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Abstract 350: Assessment of Clinicians’ Attitudes and Knowledge About Cardiac Troponin Testing

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/hcq.13.suppl_1.350 ◽

2020 ◽

Vol 13 (Suppl_1) ◽

Author(s):

Sandeep Jain ◽

Andrew Hammes ◽

Eric Rudofker ◽

Karen Ream ◽

Andrew E Levy

Keyword(s):

Myocardial Infarction ◽

Cardiac Troponin ◽

Myocardial Injury ◽

The United States ◽

Advanced Practice ◽

Attitudes And Knowledge ◽

Universal Definition ◽

Definition Of ◽

Attending Physicians

In the United States, the positive predictive value (PPV) of cardiac troponin for type 1 myocardial infarction is substantially lower than in Europe (15% vs. 50%). Further, even with publication of the 4 th Universal Definition of Myocardial Infarction, recent studies have shown that inaccurate classification of myocardial injury is common among clinicians in the United States. These findings are at least partly attributable to clinicians’ knowledge and attitudes about cardiac troponin testing; a survey of these parameters has never been conducted. Clinicians at the University of Colorado completed a brief 8-question multiple-choice survey related to troponin use, definitions of myocardial infarction and clinical assessment of elevated troponin levels. The survey was distributed via secure email and administered electronically using the Qualtrics™ platform. Responses were anonymous, completion was estimated to take 3 minutes and a lottery award system was used as an incentive for participation. Respondents included trainees, advanced practice providers and attending physicians from internal medicine, emergency medicine and medical subspecialties. We plan to obtain a total of 300 responses with descriptive findings of preliminary results included below. The survey was completed by 114 clinicians: 37 interns (32%), 45 residents (39%), 9 advanced practice providers (8%), 11 fellows (10%), and 12 attending physicians (11%). Regarding indications for troponin testing, 93% (106/114) indicated that they “usually” or “always” check troponin levels in patients with chest pain. More interestingly, 46% (52/112) reported checking troponin on “undifferentiated patients” at least half the time. For troponin interpretation, 97% (110/114) of participants identified that troponin levels alone cannot rule in or rule out coronary artery disease. In contrast, only 36% (41/114) and 55% (63/114), respectively, identified the NPV and PPV of a contemporary troponin assay for type 1 MI. Further, only 50% (57/114) of respondents identified that the likelihood of type 1 MI increases as troponin levels increase. Three brief clinical vignettes revealed that, while 78% (89/114) and 74% (45/61) of participants, respectively, identified type 1 MI and type 2 MI presentations, only 40% (21/53) of respondents correctly identified a vignette for non-ischemic myocardial injury. Concordant with this finding, 54% (61/114) of clinicians correctly identified the 4 th Universal Definition of Myocardial Infarction. These preliminary findings highlight important facets of clinician attitudes and knowledge about troponin testing that help explain the poor PPV for troponin and diagnostic misclassification observed among U.S. clinicians. These results could help guide curricular and clinical decision support interventions designed to improve the use and interpretation of cardiac troponin testing.

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Understanding cardiac troponin part 1: avoiding troponinitis

Emergency Medicine Journal ◽

10.1136/emermed-2017-206812 ◽

2017 ◽

Vol 35 (2) ◽

pp. 120-125 ◽

Cited By ~ 8

Author(s):

Richard Body ◽

Edward Carlton

Keyword(s):

Myocardial Infarction ◽

Coronary Artery Disease ◽

Cardiac Troponin ◽

Myocardial Injury ◽

Supply And Demand ◽

Clinical Context ◽

Serial Sampling ◽

Artery Disease

Cardiac troponin (cTn) is a highly specific biomarker of myocardial injury and is central to the diagnosis of acute myocardial infarction (AMI). By itself, however, cTn cannot identify the cause of myocardial injury. ‘Troponinitis’ is the condition that leads clinicians to falsely assign a diagnosis of AMI based only on the fact that a patient has an elevated cTn concentration. There are many causes of myocardial injury other than AMI. Clinicians are required to differentiate myocardial injury caused by AMI from other causes.In part 1 of this series on cTn, we provide a structured overview to help practising clinicians to interpret ‘positive’ cTn results appropriately. There are three core principles. First, when reviewing a cTn result, clinicians must carefully consider the clinical context. Only this can distinguish primary (termed type 1) AMI caused by coronary artery disease from secondary (termed type 2) AMI caused by another condition with an imbalance in the supply and demand of oxygen to the myocardium. Second, clinicians must consider the patient’s baseline condition in order to determine the presence or absence of factors that may predict a chronic cTn elevation. Third, clinicians should routinely use serial sampling to detect a change of cTn that is expected in patients with acute (rather than chronic) myocardial injury. Using these simple principles, clinicians can avoid underdiagnosis and overdiagnosis of AMI.

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Treatment and outcomes of type 2 myocardial infarction and myocardial injury compared with type 1 myocardial infarction

Coronary Artery Disease ◽

10.1097/mca.0000000000000545 ◽

2018 ◽

Vol 29 (1) ◽

pp. 46-52 ◽

Cited By ~ 9

Author(s):

Nathaniel R. Smilowitz ◽

Pritha Subramanyam ◽

Eugenia Gianos ◽

Harmony R. Reynolds ◽

Binita Shah ◽

...

Keyword(s):

Myocardial Infarction ◽

Myocardial Injury

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Abstract 17382: Gender Difference in Presentation, Management and Outcome of Patients With Acute Myocardial Infarction: A Sub-analysis of J-MINUET Study

Circulation ◽

10.1161/circ.132.suppl_3.17382 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Yasuharu Nakama ◽

Masaharu Ishihara ◽

Masashi Fujino ◽

Hisao Ogawa ◽

Koichi Nakao ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Gender Difference ◽

Hospital Mortality ◽

Current Smoking ◽

Killip Class ◽

Universal Definition ◽

The Impact

Purpose: Several studies have reported gender difference in presentation, management and outcome in patients with acute myocardial infarction (AMI). In this study, we focused the impact of age on gender difference in mortality after AMI. Methods: Between July 2012 and March 2014, 3283 patients were admitted to the 28 hospitals participating to the J-MINUET group within 48 hours after the onset of AMI. AMI was diagnosed by universal definition (type 1 or type 2). Patients were divided into 5 strata according to their age: those with age <55 years, 55-64 years, 65-74 years, 75-84 years and ≥85 years. Results: There were 813 women (24.8%). Women were significantly older than men (74.5±11.8 years vs 66.6±12.3 years, P<0.001). Women had longer time from onset to admission, more NSTEMI, atypical symptom other than chest pain, Killip class ≥2, CKD and type 2 MI. They also had less diabetes and current smoking habits. Although most of the patients received urgent angiography (93.1%), it was less frequent in women (90.4% vs 94.0%, P<0.001). Among patients who underwent primary PCI (85.1%), achievement of final TIMI-3 flow was similar (91.2% vs 92.0%, P=0.53). In-hospital mortality was significantly higher in women than men (9.6% vs 5.5%, P<0.001). When patients were stratified according to their age, there was a liner increase in the prevalence of women as age advanced: 10.6% in <55 years, 15.1% in 55-64 years, 19.8% in 65-74 years, 35.6% in 75-84 years and 53.6% in ≥85 years (P<0.001). There was no significant gender difference in mortality in each stratum (Figure). Multivariate analysis showed that women was no more an independent predictor of death after adjusting age (OR 1.29, 95%CI 0.95-1.75, P=0.10), or age and other variables (OR 1.19, 95%CI 0.79-1.76, P=0.40). Conclusions: Women had higher in-hospital mortality than men after AMI even in the contemporary troponin era. However, their high mortality was mostly explained by their advanced age.

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Universal Definition of Myocardial Infarction: Clinical Insights

Cardiology ◽

10.1159/000371739 ◽

2015 ◽

Vol 131 (1) ◽

pp. 13-21 ◽

Cited By ~ 16

Author(s):

Luis Paiva ◽

Rui Providência ◽

Sérgio Barra ◽

Paulo Dinis ◽

Ana C. Faustino ◽

...

Keyword(s):

Myocardial Infarction ◽

Detailed Comparison ◽

Term Survival ◽

Acute Ischaemia ◽

Universal Definition ◽

Definition Of

Aims: The universal definition of myocardial infarction (MI) classifies acute ischaemia into different classes according to lesion mechanism. Our aim was to perform a detailed comparison between these different types of MI in terms of baseline characteristics, management and prognosis. Methods and Results: An observational retrospective single-centre cohort study was performed, including 1,000 consecutive patients admitted for type 1 (76.4%) or type 2 MI (23.6%). Type 2 MI patients were older, had a higher prevalence of comorbidities and worse medical status at admission. In-hospital mortality did not differ significantly between the MI groups (8.8 vs. 9.7%, p = 0.602). However, mortality during follow-up was almost 3 times higher in type 2 MIs (HR 2.75, p < 0.001). Type 2 MI was an independent all-cause mortality risk marker, adding discriminatory power to the GRACE model. Finally, important differences in traditional risk score performances (GRACE, CRUSADE) were found between both MI types. Conclusions: Several important baseline differences were found between these MI types. Regarding prognosis, long-term survival is significantly compromised in type 2 MIs, potentially translating patients' higher medical complexity and frailty. Distinction between type 1 and type 2 MI seems to have important implications in clinical practice and likely also in the results of clinical trials.

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Cardiac Troponin Thresholds and Kinetics to Differentiate Myocardial Injury and Myocardial Infarction

Circulation ◽

10.1161/circulationaha.121.054302 ◽

2021 ◽

Author(s):

Ryan Wereski ◽

Dorien M. Kimenai ◽

Caelan Taggart ◽

Dimitrios Doudesis ◽

Kuan Ken Lee ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Troponin ◽

Myocardial Injury ◽

Troponin I ◽

Controlled Trial ◽

Rate Of Change ◽

Coronary Syndrome ◽

Diagnostic Threshold

Background: Whilst the 99th percentile is the recommended diagnostic threshold for myocardial infarction, some guidelines also advocate the use of higher troponin thresholds to rule-in myocardial infarction at presentation. It is unclear whether the magnitude or change in troponin concentration can differentiate causes of myocardial injury and infarction in practice. Methods: In a secondary analysis of a multi-centre randomized controlled trial, we identified 46,092 consecutive patients presenting with suspected acute coronary syndrome without ST-segment elevation myocardial infarction. High-sensitivity cardiac troponin I concentrations at presentation and on serial testing were compared between patients with myocardial injury and infarction. The positive predictive value (PPV) and specificity were determined at the sex-specific 99th percentile upper reference limit (URL), and rule-in thresholds of 64 ng/L and 5-fold of the URL for a diagnosis of type 1 myocardial infarction. Results: Troponin was above the 99th percentile in 8,188 (18%) patients. The diagnosis was type 1 or type 2 myocardial infarction in 50% and 14%, and acute or chronic myocardial injury in 20% and 16%, respectively. Troponin concentrations were similar at presentation in type 1 (median [25th percentile - 75th percentile] 91 [30-493] ng/L) and type 2 (50 [22-147] ng/L) myocardial infarction, and in acute (50 [26-134] ng/L) and chronic (51 [31-130] ng/L) myocardial injury. The 99th percentile and rule-in thresholds of 64 ng/L and 5-fold URL gave a PPV of 57% (95% confidence interval [CI] 56-58%), 59% (58-61%) and 62% (60-64%), and a specificity of 96% (96-96%), 96% (96-96%) and 98% (97-98%), respectively. The absolute, relative and rate of change in troponin concentration was highest in patients with type 1 myocardial infarction (P<0.001 for all). Discrimination improved when troponin concentration and change in troponin were combined compared to troponin concentration at presentation alone (area under curve, 0.661 [0.642-0.680] versus 0.613 [0.594-0.633]). Conclusions: Although we observed important differences in the kinetics, cardiac troponin concentrations at presentation are insufficient to distinguish type 1 myocardial infarction from other causes of myocardial injury or infarction in practice and should not guide management decisions in isolation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01852123

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Troponin elevation pattern and subsequent cardiac and non-cardiac outcomes: Implementing the Fourth Universal Definition of Myocardial Infarction and high-sensitivity troponin at a population level

PLoS ONE ◽

10.1371/journal.pone.0248289 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0248289

Author(s):

Anthony (Ming-yu) Chuang ◽

Mau T. Nguyen ◽

Ehsan Khan ◽

Dylan Jones ◽

Matthew Horsfall ◽

...

Keyword(s):

Myocardial Infarction ◽

Ventricular Arrhythmia ◽

Myocardial Injury ◽

High Sensitivity ◽

Cardiac Outcomes ◽

High Sensitivity Troponin ◽

Acute Myocardial Injury ◽

Acute Mi ◽

Universal Definition ◽

Definition Of

Background The Fourth Universal Definition of Myocardial Infarction (MI) differentiates MI from myocardial injury. We characterised the temporal course of cardiac and non-cardiac outcomes associated with MI, acute and chronic myocardial injury. Methods We included all patients presenting to public emergency departments in South Australia between June 2011–Sept 2019. Episodes of care (EOCs) were classified into 5 groups based on high-sensitivity troponin-T (hs-cTnT) and diagnostic codes: 1) Acute MI [rise/fall in hs-cTnT and primary diagnosis of acute coronary syndrome], 2) Acute myocardial injury with coronary artery disease (CAD) [rise/fall in hs-cTnT and diagnosis of CAD], 3) Acute myocardial injury without CAD [rise/fall in hs-cTnT without diagnosis of CAD], 4) Chronic myocardial injury [elevated hs-cTnT without rise/fall], and 5) No myocardial injury. Multivariable flexible parametric models were used to characterize the temporal hazard of death, MI, heart failure (HF), and ventricular arrhythmia. Results 372,310 EOCs (218,878 individuals) were included: acute MI (19,052 [5.12%]), acute myocardial injury with CAD (6,928 [1.86%]), acute myocardial injury without CAD (32,231 [8.66%]), chronic myocardial injury (55,056 [14.79%]), and no myocardial injury (259,043 [69.58%]). We observed an early hazard of MI and HF after acute MI and acute myocardial injury with CAD. In contrast, subsequent MI risk was lower and more constant in patients with acute injury without CAD or chronic injury. All patterns of myocardial injury were associated with significantly higher risk of all-cause mortality and ventricular arrhythmia. Conclusions Different patterns of myocardial injury were associated with divergent profiles of subsequent cardiac and non-cardiac risk. The therapeutic approach and modifiability of such excess risks require further research.

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