• Women, AMI, and Missed Diagnoses – All in the Symptoms?

    ‘Typical’ AMI symptoms occurred in only 1% of women studied

    A new study may go far to help explain why acute myocardial infarction (AMI) is missed more frequently in women than in men. When presenting with AMI, women have substantially more variation in unique symptom phenotypes, broader distribution of symptom phenotype subgroups, and a higher number of symptoms per patient than men. 

    VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) is the largest prospective observational study of young women and men with AMI (18–55 years). In a secondary analysis, John E. Brush Jr., MD, of Eastern Virginia Medical School, Norfolk, and colleagues conducted a systematic analysis of records and structured patient interviews from the VIRGO participants.

    Their study, published in Circulation: Cardiovascular Quality and Outcomes, appears to be the first to look at how symptoms combine at the individual level as symptom phenotypes and how those symptom-phenotype subgroups are distributed in women and men. (Prior studies of patients with AMI have reported how symptoms of AMI are distributed at the population level, not how symptoms combine at the individual level as unique symptom phenotypes.)

    Women had significantly more symptom phenotypes than men, whether culled from patient interviews (426 vs. 280) or abstracted from the medical record (244 vs. 154), both highly statistically significant. Also, uncommon phenotypes were more common in women.

    “These findings may have substantial clinical implications,” Brush told CRTonline. “The added phenotypes in women could create more diagnostic confusion and ambiguity for women than men and could be a factor to explain why the diagnosis of AMI is missed more commonly in women.”

    Women were more likely to have a non-STEMI (p < 0.001), less likely to receive emergent or urgent percutaneous coronary intervention (p = 0.006), more likely to have atypical chest pain (p < 0.001), and more likely to have a delay from symptom onset to presentation, the latter of which could certainly be impacted by the ambiguity around the diagnosis.

    Think about that term: atypical chest pain. In a commentary accompanying the VIRGO paper, Nakela Cook, MD, MPH, of the National Heart, Lung and Blood Institute, wrote that it is time to “acknowledge that symptoms more frequently experienced by 50% of the population are not atypical at all but rather the constellation of symptoms experienced by a specific segment of our population.”


    Teaching the Stereotype

    Brush noted that textbooks teach the prototype for a diagnosis, which is an imaginary patient who has the 4 or 5 most common symptoms. For AMI, the classic prototype is chest pain, radiating to the arm, neck or back, with shortness of breath and sweating. He said, “Interestingly, those symptoms and only those symptoms occurred as a phenotype in only 1% of the VIRGO patients.”

    “Teaching students the prototype is a way of reminding them about the most common features,” said Brush, “but it is actually teaching them a stereotype since that particular combination occurs as a phenotype fairly rarely.”

    Consequently, Brush thinks the VIRGO results have implications for training medical students.

    “They should be taught to think more expansively when they are trying to recognize the diagnosis of AMI in women,” he said.



    Brush Jr. JE, Krumholz HM, Greene EJ, et al. Sex Differences in Symptom Phenotypes Among Patients With Acute Myocardial Infarction. Circ Cardiovasc Qual Outcomes 2020;13:e005948.


    Cook NL. Embracing Differences to Advance a Contemporary Understanding of Symptom Phenotypes in Acute Myocardial Infarction. Circ Cardiovasc Qual Outcomes 2020;13:e006431. DOI: 10.1161/CIRCOUTCOMES.120.006431 https://www.ahajournals.org/doi/10.1161/CIRCOUTCOMES.120.006431

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