What Kind of Heart Attack?

A woman in her 50s arrives at a hospital’s emergency department short of breath, complaining of nausea and pain in her jaw.

Although the woman feels no chest pain, the attending physician immediately suspects a heart attack. Because even though chest pain or discomfort are the most common symptoms of a heart attack in women and men, women are more likely to experience other symptoms, such as shortness of breath, nausea, lightheadedness, or pain in the jaw, arms, or back.

Similarly, among young women diagnosed with a heart attack, routine cardiac tests often do not reveal the typical findings of a heart attack — a blockage in the heart artery. There may be no blockages, or there may be other problems in the heart artery. In many instances, doctors do not know what caused the heart attack. Yet these nuances are not fully incorporated into the current classification system used to define different types of heart attacks. And so the diagnostic systems that currently exist may fall short of the gender-specific accuracy necessary to provide the best individualized treatment possible.

“For people who come to the hospital with a possible heart attack, all sirens go off and we activate a common set of clinical pathways to diagnose and treat,” said Dr. Erica S. Spatz, a general cardiologist and a clinical investigator at Yale’s Center for Outcomes Research and Evaluation (CORE). “But many young women, do not have the classic features of a heart attack, thus creating uncertainty about what is going on and how to classify the condition, and how best to treat it going forward. Yet despite the differences, we tend to group everyone together.”

Acute myocardial infarction (AMI), the technical term for a heart attack, occurs when blood flow to the heart is blocked so as to damage the muscle and potentially cause death. The condition leads to the hospitalization of about 40,000 women each year in the United States.

The typical mechanism for causing a heart attack is the rupture of a plaque or a blood clot in an artery. Plaques are waxy substances created by damage to the arterial wall, blocking blood flow needed to supply the heart with oxygen. Risk factors for plaque include smoking, high blood pressure, and high cholesterol. About one in five young women do not show evidence of a plaque rupture or a blood clot in an artery.

And yet women are grouped into classification systems that can obscure some patients’ disease processes while not accounting for some others.

With the help of a grant from Women’s Health Research at Yale, Dr. Spatz has begun testing a new method of sorting women who have had heart attacks into categories that more fully describe the ways in which women develop problems that might lead to a heart attack.

“Giving people a diagnosis or a label for their symptoms and disease course validates what they’ve experienced,” Spatz said. “And it provides the scientific community with a common language to communicate with one another about the distinct features of a disease, which can ultimately stimulate research and discovery of biological mechanisms and best practices to improve outcomes.”

The current classification system, known as the Third Universal Definition of MI, includes five categories of patient types:

• Type 1 describes patients with a plaque rupture.
• Type 2 involves a condition other than coronary artery disease (the plaque-caused hardening of arteries) contributing to an imbalance between the heart’s oxygen supply and demand, such as bleeding or a stroke.
• Type 3 describes death of heart muscle with symptoms suggesting a lack of oxygen (ischemia).
• Type 4a includes problems related to a non-surgical procedure called percutaneous coronary intervention (PCI) in which a thin flexible tube (catheter) is used to place a structure called a stent in the artery to open it up.
• Type 4b describes a condition called stent thrombosis in which a life-threatening blood clot forms on a stent.
• Type 5 involves complications from a surgery called coronary artery bypass graft (CABG) in which a healthy artery is connected to a blocked one, creating a new path for oxygen-rich blood to reach the heart.

But some symptoms and mechanisms of disease that are more common in women simply do not fit in this system.

“As a doctor, you take into account all the nuances of your patient to give the most fitting diagnosis and best estimates for treatment and prognosis,” Spatz said. “But sometimes we don’t have any evidence to support that labelling or those recommendations.”

Spatz’s team developed a new scheme based on a study funded by the National Institutes of Health called Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) and using clinical data describing patient symptoms and findings after the insertion of a catheter through blood vessels to evaluate heart function.

The researchers classified 2,802 men and women under 55 years old into five classes:

• Class 1 describes a plaque rupture.
• Class 2a includes obstructive coronary artery disease with a mismatch in heart muscle oxygen demand and supply.
• Class 2b includes obstructive coronary artery disease without an oxygen supply-demand mismatch.
• Class 3a involves non-obstructive coronary artery disease with an oxygen supply-demand mismatch.
• Class 3b involves non-obstructive coronary artery disease without an oxygen supply-demand mismatch.
• Class 4 covers some other identifiable mechanism such as spontaneous tearing of the artery wall, a sudden spasm leading to tightening of a blood vessel and lowering its flow rate, or a blockage caused by a blood clot, a globule of fat, gas, or an outside object (embolism).
• Class 5 is for an undetermined cause.

Comparing the two classification systems, Spatz found that about 13 percent of women were unable to be classified using the traditional Third Universal Definition. The VIRGO taxonomy she helped create left out less than 1 percent of patients.

“People with Type 2 AMI can be very different from one another, yet we tend to treat them the same,” Spatz said of the older, more established classification system. “Maybe we can do better.”

The new WHRY-funded study will group patients with heart attack from other existing registries into the VIRGO categories, allowing Spatz’s team to refine and validate the taxonomy in other populations and to assess outcomes associated with different classes of heart attack among women of different ages, races and ethnicities, and between women and men.

Spatz aims to develop a system that clinicians can use when evaluating and treating patients that is more precisely attuned with their individual condition. For example, patients with an oxygen supply-demand imbalance may benefit from a different set of tests and different medication types. The Women’s Health Research at Yale Pilot Project Program is supported in part by the Maximilian E. and Marion O. Hoffman Foundation, the Seymour L. Lustman Memorial Fund, The Seedlings Foundation, The Werth Family Foundation, and anonymous donors.

She anticipates the possible need to add classifications and hopes to expand the project to other hospitals to try to capture as many different types of cases as possible.

“As we move to more personalized medicine, we need to develop new methods that incorporate people’s unique clinical conditions and the context in which they present,” Spatz said. “This approach is especially important in women and in individuals of different ethnic backgrounds who may not exhibit the classic disease course.”

Spatz grew up in Staten Island, N.Y., always aware of diversity and how different people experience different health problems. She hopes her study will serve as a tool that can offer more precision and equity in medicine to better serve diverse populations, particularly when unexpected symptoms appear in women and minorities.

“We so often say it’s atypical or nonclassic, and then we stop there,” Spatz said. “I think that once it has a name, people are much more inclined to see it, diagnose it, and start to investigate ways to treat it.”

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