Expert consensus on the classification of acute atherothrombotic myocardial infarction by stage of tissue injury severity

Myocardial infarction (MI) causes millions of deaths worldwide. Though there have been advances in the survival rates following ST-elevation MI (STEMI), survivors often develop heart failure due to ischemic cardiomyopathy. Diagnostic standards and risk scores are thus of importance in improving patient management in this area. A document published in the Canadian Journal of Cardiology outlines the Canadian Cardiovascular Society's classification of acute MI. 

Study: The Canadian Cardiovascular Society Classification of Acute Atherothrombotic Myocardial Infarction Based on Stages of Tissue Injury Severity: An Expert Consensus Statement. Image Credit: SaiArLawKa2/Shutterstock.com
Study: The Canadian Cardiovascular Society Classification of Acute Atherothrombotic Myocardial Infarction Based on Stages of Tissue Injury Severity: An Expert Consensus Statement. Image Credit: SaiArLawKa2/Shutterstock.com

Classification systems

Risk scores and disease classifications are important to predict adverse events and decide the level of care or monitoring required, as well as build algorithms for treatment. The data from such tools are fundamental to further research that helps improve the outcomes.

One classification system is the “universal definition of MI” which divides these events into STEMI and non-STEMI (NSTEMI), based on the electrocardiography (ECG) findings. “ST-elevation is a well-established marker of very high risk, with an indication for immediate reperfusion therapy.”

There are also clinical systems like the Thrombolysis in Myocardial Infarction (TIMI) risk score, the Killip classification, and the History, ECG, Age, Risk factors, Troponin (HEART) score.

These do not consider the myocardial damage that causes cardiac remodeling, especially of the ventricles. Thus, they do not predict sequelae like heart failure, arrhythmias, or hospitalization, nor mortality from prior MI. This shows the need for newer tools incorporating tissue damage.  

MI pathophysiology

With acute MI due to atherosclerosis-induced clots within the coronary arteries, the heart muscle undergoes necrosis in the shape of a wavefront beginning at the blocked artery and covering the area supplied by it.

Current treatment focuses on reperfusion, or restoring blood supply to this area, arresting the advance of this wave and thus rescuing myocardium that is not yet critically damaged. The final size of the infarcted or dead myocardium region is thus reduced, lowering the risk of future heart failure and death.

Other forms of tissue damage have also been observed, such as myocardial edema, accompanying or preceding necrosis, and microvascular damage, blocking these vessels and often resulting in hemorrhage.

Based on these findings obtained by advanced imaging techniques including Cardiovascular Magnetic Resonance (CMR) imaging, the ischemia/reperfusion injury cascade has been described, showing four sequential stages through which myocardial damage occurs in reperfused myocardium.

This laid the foundation of the current classification by the Canadian Cardiovascular Society (CCS). Hopefully, it will help better risk prediction, accurate documentation, and interventions for improved tissue healing.

CCS stages

The four stages of reperfusion injury are myocardial edema, necrosis, microvascular obstruction (MVO), and finally, myocardial hemorrhage. Each of these stages causes progressively more severe injury to the heart, causing the prognosis to become worse.

The CCS stages thus include stage 1, with edema; stage 2, with additional necrosis; stage 3, with microvascular obstruction as well; and stage 4, with myocardial hemorrhage plus the above three. The presence of hemorrhage is associated with mechanical complications, corroborating the status of this stage as the most serious type of MI.

This indicates the crucial need to begin early reperfusion treatment before ischemia is prolonged, thus maximizing the potential for almost complete prevention of necrosis. Tissue-level perfusion is best assessed by myocardial contrast echocardiography and CMR, whereas epicardial coronary artery flow is assessed on coronary angiography.

CCS stage 1

The CCS statement reconsiders the definition of aborted MI (stage 1), which has traditionally been based on changes in serum markers and ECG tracings. Reperfusion within 4 hours of the onset of ischemic symptoms, but especially within 1-2 hours, is associated with the highest effectiveness in aborting MI, leading to the popular concept of the “golden hour” of reperfusion to avoid significant heart damage following an MI.

Fibrinolysis before reaching the hospital is more markedly associated with aborted MI than primary percutaneous intervention is. Aborted MI makes up about 5-15% overall but up to 30% among those treated within an hour of ischemia. In about half the cases, no necrosis results, with minor damage in the rest.

The prognosis is good in CCS stage 1, with 5% or less developing adverse events, many times lower than the rate in nonaborted MI.

CCS stage 2

In CCS stage 2, complete salvage is no longer possible, and myocardial necrosis has occurred to a significant degree. However, the vascular bed remains intact, with normal tissue perfusion after the epicardial block is resolved. Following stage 2, infarct size increases, and regional wall motion abnormality (RWMA) is visible on echocardiography.

From 30% to 50% of MIs are in this stage.

CCS stage 3

CCS stage 3 includes the earliest stage of reperfusion injury, with the injury extending beyond the epicardial layer. Along with CCS stage 4, it includes 40% to 60% of MI patients. Here, cardiomyocyte necrosis is coupled with microvascular bed injury, causing MVO.

In MVO, microvascular ischemia causes swelling of the endothelial cells with capillary compression and endothelial activation. As a result, the lumen of the small vessels is blocked by blood cells, preventing the restoration of flow in the distal coronary artery, as seen in coronary angiography.

It has been shown by CMR that finding reduced or no reflow increases the odds of adverse outcomes after reperfusion, independent of infarct size. MVO may comprise over half of all reperfused MI patients.

CCS stage 4

CCS stage 4 is the most severe form of myocardial ischemia-reperfusion injury caused by sustained serious ischemia. The capillaries weaken, and with the restoration of blood flow, they rupture, releasing blood into the myocardium. Intramyocardial hemorrhage is thus characteristic of CCS stage 4 and is closely correlated with mechanical complications.

The resulting presence of ferric iron crystals in the infarcted tissue provokes prolonged inflammation, fatty degeneration of cardiac muscle, and perhaps ventricular arrhythmia. Thus, the infarct size doubles after reperfusion, with poor left ventricular systolic function.

Conclusion

The CCS consensus statement captures the four stages of MI based on tissue damage, which causes progressive damage according to the wavefront hypothesis of ischemic cardiomyocyte death of Reimer and Jennings. This differentiates patients at high risk for mechanical complications and infarct expansion from those at low risk.

While not ready for clinical use, it promotes further directed clinical research on cardioprotective therapies specific for each stage by providing outcome measures and end points for research, as well as identifying therapeutic targets.

It is hoped that this document will serve as a starting point for continued clinical and scientific refinement to help define our present understanding of acute atherothrombotic MI.”

Journal reference:
Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.

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