ATLANTA, GA — Patients presenting with STEMI and current or recent COVID-19 infection often do not have a culpable lesion, with women being more likely than men to have this, a pre-specified analysis North American COVID-19 Myocardial Infarction (NACMI) registration shows.

One-third of women and 18% of men had no causative lesion detectable on angiography, a finding the researchers call “startling” given that MIs with non-obstructive coronary arteries (MINOCA) typically have only 3, Constitutes 5% to 6.5% of all real-world STEMIs.

“MINOCA is always higher in women than in men. We know this from before COVID,” study lead author Odayme Quesada, MD (The Christ Hospital Women’s Heart Center, Cincinnati, OH) told TCTMD. “But COVID-19 is clearly playing a role in dramatically increasing rates of these non-culpable STEMIs in both women and men, and the question is why.” Quesada presented the findings today at the 2022 Scientific Sessions of the Society for Cardiovascular Angiography and Interventions (SCAI) before.

COVID-19 is clearly playing a role in dramatically increasing the rates of these non-culpable STEMIs, and the question is why. Odayme Quesada

Since the early days of the pandemic, there have been uncertainties about how the virus contributes to systemic inflammation, with many patients found to be at increased risk of arterial or venous thrombotic complications. Quesada and colleagues say microvascular thrombosis and/or embolization is a possible mechanism for STEMI in patients with COVID-19 infection and no causative lesion. Other possible causes range from stress cardiomyopathy associated with serious illness to disruption of coronary artery plaques, epicardial coronary spasm, spontaneous coronary artery dissection, and nonischemic cardiomyopathy.

Quesada and her group don’t call these findings MINOCA — because they’re unsure if they’re genuine MINOCA patients — preferring to refer to them as “not guilty” STEMIs until they get a better understanding of what’s going on .

Commenting on TCTMD, Herb D. Aronow, MD, MPH (Henry Ford Health, Detroit, MI) called the mysterious results “thought-provoking.” a MINOCA-like STEMI. Both Quesada and Aronow said until more data is available, the possibility of “COVID MINOCA” cannot be completely ruled out.

“We have so little angiographic data on men and women with COVID and myocardial infarction,” Aronow said. “The NACMI registry has taught us a lot about epidemiology, . . . but there is definitely more to learn.”

Analyzing gender differences

The NACMI Registry is a collaboration between SCAI, the American College of Cardiology and the Canadian Association of Interventional Cardiology, which includes STEMI patients hospitalized with COVID-19 from 64 medical centers in North America.

For the latest analysis, which focused on gender differences, Quesada and colleagues examined hospital mortality in 585 patients (26.3% female) admitted between March 2020 and late December 2021. All had tested positive for COVID-19 during or within the study 4 weeks prior to their Index STEMI hospitalization. Compared to men, women were older and more likely to have pre-existing diabetes and a history of stroke or TIA. All other risk factors were similar in males and females, and no significant gender differences were found in pre-PCI cardiac arrest, cardiogenic shock, or left ventricular ejection fraction.

Primary or emergency PCI was performed more frequently in men than in women (76% vs. 61%; P = 0.002), with women more likely to receive medical therapy (33% vs. 20%; P = 0.003). There were no gender differences in mean length of stay, proportion of CABG, use of thrombolytics, or door-to-balloon time.

The NACMI registry has taught us a lot about epidemiology, . . . but there is definitely more to learn. Herb Aronow

Overall, 33% of women and 27% of men died in hospital (P = 0.22), with no significant gender differences in stroke, reinfarction, or the composite endpoint of hospital death, stroke, or reinfarction. Adjustments for angiographic and clinical factors did not alter the results.

The high death rates are consistent with previous reports from a larger NACMI cohort showing a 33% mortality rate in both men and women with STEMI and COVID.

Aronow added that while the NACMI data is “fairly representative” of clinical experience with STEMI in the context of COVID, the number of patients is too small to draw firm conclusions. However, he noted that the registry appears to show an interesting shift away from chest pain and toward dyspnea as the dominant symptom for women, rather than chest pain, which was the pre-COVID dominant symptom for both sexes. Women in NACMI presented dyspnea at a rate of 56% compared to 45% in men (P = 0.02).

However, Aronow warned that “the jury is still out on whether there really are differences in outcomes between men and women with COVID who have a myocardial infarction.”

Looking for additional insights

In an editorial accompanying the study, Mirvat Alasnag, MD (King Fahd Armed Forces Center, Jeddah, Saudi Arabia) and colleagues say that understanding the root causes of MINOCA in COVID will require ongoing work and from the use of intracoronary imaging, provocation testing, heart -MRI and thrombophilia assays.

“Although NACMI does not make an assessment of outcomes, it is a representation of disease patterns and practice trends,” they write. “The NACMI-Sex sub-study provides an incentive to better understand MINOCA and to urge clinicians to investigate these cases more closely.” Importantly, as the registry continues to grow, Alasnag and colleagues say, “Analyzing results by race/ethnic Affiliation and gender may provide additional insights into potential differences in care.”

Quesada said the next step is a core lab analysis to find out if they are genuine MINOCAs or MINOCA knockoffs. “We just don’t know enough at this point to say for sure,” she added. It will also be important to enroll enough vaccinated patients in the registry to compare their results with patients in the early stages of the pandemic. Only 22 patients in the current analysis were vaccinated and none of them died, previously reported in another NACMI analysis that showed an approximately 25% decrease in hospital mortality between 2020 and 2021.

Given observations of STEMI mimics in COVID patients, panelist Jacqueline Tamis-Holland, MD (Icahn School of Medicine at Mount Sinai, New York, NY) asked if any of the patients with the MINOCA-like STEMIs had a cardiac MRI, to distinguish whether there might be non-ischemic mechanisms at play.

Quesada said given the COVID-positive status of these patients, chances are slim many cardiac MRIs were done, but the echocardiographic data will help determine how many could be takotsubo.

Panelist Dr. Gregg Stone (Icahn School of Medicine at Mount Sinai) added that while the study raises a variety of questions, he believes some of the cases are Type 2 MIs or demand ischemia MIs could. Quesada said this issue is addressed by evaluating the EKGs to confirm they are true ST elevations occurred.