Sex-specific VIRGO taxonomy better classifies women with MI

Nearly one in six young women who suffer a heart attack can’t be classified under the Fourth Universal Definition of MI, according to a study out of Yale University—but the majority can be accurately classified using a sex-specific taxonomy known as VIRGO.

A team led by Erica Spatz, MD, an associate professor of cardiology at Yale and the paper’s senior author, said the fourth and latest Universal Definition of MI—announced last August at the European Society of Cardiology Congress in Munich—continues to ignore the fact that women and men often present with entirely different symptoms of MI.

“A significant proportion of women under 55 years of age do not fall into the classic categories of plaque rupture and myocardial oxygen supply-demand mismatch, the distinguishing characteristics between Types 1 and 2 AMI by the Fourth Universal Definition,” the authors wrote in the International Journal of Cardiology. “Many women have non-obstructive coronary artery disease (CAD) without an obvious trigger for ischemia.”

So instead of the industry standard, Spatz and colleagues turned to the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) taxonomy, a more inclusive system that was previously established as part of another study. VIRGO distinguishes four phenotypic classes and a fifth class for indeterminate cases:

  • Class I: Critical stenosis or thrombosis defined as >70% stenosis, fractional flow reserve <0.8 or thrombosis on angiogram
  • Class II: >50% stenosis in at least one epicardial vessel without critical stenosis or thrombosis
    • IIa: Evidence of supply-demand mismatch
    • IIb: No evidence of supply-demand mismatch
  • Class III: <50% stenosis in the epicardial vessels
    • IIIa: Evidence of supply-demand mismatch
    • IIIb: No evidence of supply-demand mismatch
  • Class IV: A specific alternate mechanism other than plaque rupture as diagnosed during angiography (could be spontaneous coronary artery dissection, vasospasm, coronary embolism or stress-induced cardiomyopathy)
  • Class V: Indeterminate cases

Spatz et al. examined the medical records of women who presented to a single center for acute MI between January 2013 and September 2016 and underwent cardiac catheterization during their index visit. The team then used both the current Universal Definition of MI and the VIRGO taxonomy to classify the women’s conditions.

They found nearly one in six women who had a heart attack couldn’t be classified under the universal definition, largely because that definition fails to account for certain mechanisms that are more common in women, like arterial spasms or tears that inhibit blood flow to the heart without the presence of plaque obstruction. The remaining 68.4% were classified as Type 1, 11.9% were classified as Type 2 and 2.3% were classified as Type 4b.

Using the VIRGO taxonomy, the majority of women (68.4%) were classified under Class I, and the rest were stratified by their presence of obstructive CAD with demand (4%) and without demand (2.3%) or non-obstructive CAD with demand (6.8%) and without demand (10.2%). A little over 7% of patients fell into Class IV, and just 1.1% remained unclassified compared to 17.5% using the universal definition.

“In clinical practice, the two taxonomies can serve different purposes,” Spatz and co-authors wrote. “The Universal Definition of MI classification system does not require angiography and thus serves as an important initial tool in the stratification and management of patients with acute MI. The VIRGO taxonomy, on the other hand, relies on cardiac catheterization findings, which was not performed in 20% of women presenting with acute MI. Many of these women remain undiagnosed and more studies are needed to better identify clinical pathways to elucidate the underlying pathological mechanisms.”

Still, the authors said, VIRGO could be an important clinical tool for young women presenting with AMI, many of whom don’t exhibit angiographic findings consistent with the classic mechanisms of plaque rupture and thrombosis. And, seeing as how heart attacks are becoming increasingly common in younger patients, it’s worth reviewing a more tailored approach to MI classification.

“These data support the importance of adopting a more nuanced classification system into routine clinical practice, which may lead to new insights and promote research aimed to better illuminate disease mechanisms in young women, along with individualized treatment approaches to improve outcomes,” Spatz et al. wrote.


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