Classification Identifies Four Stages of Heart Attack

Fran Lowry

November 10, 2023

The Canadian Cardiovascular Society (CCS) has developed a four-stage classification

of acute atherothrombotic myocardial infarction (MI) based on the severity of the
injury to the myocardium.

Relying on more than 50 years of data on acute MI with reperfusion therapy, the
society has identified the following four stages of progressively worsening
myocardial tissue injury:

1. Aborted MI (no or minimal myocardial necrosis).

2. MI with significant cardiomyocyte necrosis but without microvascular injury.

3. Cardiomyocyte necrosis and microvascular dysfunction leading to microvascular

obstruction (that is, "no-reflow").

4. Cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage.

The classification is described in an expert consensus statement that was published

October 28 in the Canadian Journal of Cardiology.

The new classification will allow for better risk stratification and more appropriate
treatment and provide refined endpoints for clinical trials and translational research,
according to the authors.

Currently, all patients with acute MI receive the same treatment, even though they
may have different levels of tissue injury severity, statement author Andreas Kumar,
MD, chair of the writing group and associate professor of medicine at Northern
Ontario School of Medicine University in Sudbury, Ontario, Canada, told Medscape
Medical News.

"In some cases, treatment for a mild stage 1 acute MI may be deadly for someone
with stage 4 hemorrhagic MI," said Kumar.

Technological Advances

The classification is based on decades of data. "The initial data were obtained with
pathology studies in the 1970s. When cardiac MRI came around, around the year
2000, suddenly there was a noninvasive imaging method where we could investigate
patients in vivo," said Kumar. "We learned a lot about tissue changes in acute MI.
And especially in the last 2 to 5 years, we have learned a lot about hemorrhagic MI.
So, this then gave us enough knowledge to come up with this new classification."

The idea of classifying acute MI came to Kumar and senior author Rohan
Dharmakumar, PhD, executive director of the Krannert Cardiovascular Research
Center at Indiana University School of Medicine, Indianapolis, when both were at the
University of Toronto, Toronto, Ontario, Canada.
"This work has been years in the making," Dharmakumar told Medscape. "We’ve
been thinking about this for a long time, but we needed to get substantial layers of
evidence to support the classification. We had a feeling about these stages for a
long time, but that feeling needed to be substantiated."

Last year, Dharmakumar and Kumar observed that damage to the heart from MI was
not only a result of ischemia caused by a blocked artery, but also a result of bleeding
in the myocardium after the artery had been opened. Their findings were published in
the Journal of the American College of Cardiology.

The author of an accompanying editorial lauded the investigators "for providing new,
mechanistic insights into a difficult clinical problem that has an unmet therapeutic
need."

"Hemorrhagic MI is a very dangerous injury because hemorrhage itself causes a lot

of problems," said Kumar. "We reported that there is infarct expansion after
reperfusion, so once you open up the vessel, the heart attack actually gets larger.
We also showed that the remodeling of these hearts is worse. These patients take a
second hit with hemorrhage occurring in the myocardium."

Classification and Staging

"The standard guideline therapy for somebody who comes into the hospital is to put
in a stent, open the artery, have the patient stay in the hospital for 48 to 72 hours,
and then be released home," said Dharmukumar. "But here’s the problem. These two
patients who are going back home have different levels of injury, yet they are taking
the same medications. Even inside the hospital, we have heterogeneity in mortality
risk. But we are not paying attention to one patient differently than the other, even
though we should, because their injuries are very different."

The CCS classification may provide endpoints and outcome measures beyond the
commonly used clinical markers, which could lead to improved treatments to help
patients recover from their cardiac events.

"We have this issue of rampant heart failure in acute MI survivors. We’ve gotten
really good at saving patients from immediate death, but now we are just postponing
some of the serious problems survivors are going to face," said Dharmukumar. "What
are we doing for these patients who are really at risk? We’ve been treating every
single patient the same way and we have not been paying attention to the very
different stages of injury."

In an accompanying editorial, Prakriti Gaba, MD, a clinical fellow in medicine at

Brigham and Women’s Hospital in Boston, Massachusetts, and Deepak L. Bhatt, MD,
MPH, director of the Mount Sinai Fuster Heart Hospital in New York, wrote, "There is
no doubt that the classification system proposed by the investigators is important
and timely, as acute MI continues to account for substantial morbidity and mortality
worldwide."

Imaging and staging could be useful in guiding appropriate therapy, Bhatt told
Medscape. "The authors’ hope, which I think is a very laudable one, is that more
finely characterizing exactly what the extent of damage is and what the mechanism
of damage is in a heart attack will make it possible to develop therapies that are
particularly targeted to each of the stages," he said.
"It is quite common to have the ability to do cardiac MRI at experienced
cardiovascular centers, although this may not be true for smaller community
hospitals," Bhatt added. "But at least at larger hospitals, this will allow for much
finer evaluation and assessment of exactly what is going on in that particular patient
and how extensive the heart muscle damage is. Eventually, this will facilitate the
development of therapies that are specifically targeted to treat each stage."