mRNA Vaccine-Linked Myocarditis Resolves in Time, Without Clinical Events

Encouraging follow-up data from two small series show that myocarditis developing after mRNA vaccination against SARS-CoV-2 does resolve, or shows signs of doing so, approximately 6 months after the initial diagnosis.

In the first series, which included nine male patients (mean age 22 years) who developed myocarditis after receiving their second Pfizer/BioNTech or Moderna vaccine dose, there was a complete resolution of late gadolinium enhancement (LGE) on cardiac MRI in one patient and resolving, although persistent, LGE in the remaining eight patients.

“After 3 to 6 months on the repeat cardiac MRI, all of the cases had resolution of myocardial edema, which means that the active inflammation is gone,” lead investigator Yash Patel, MD, MPH (Warren Alpert Medical School at Brown University, Providence, RI), told TCTMD. “In terms of clinical follow-up, none had any adverse cardiovascular outcomes. There was no repeat myocarditis, no arrhythmias, no heart failure, and no hospitalizations.”

In the second report, which was based on seven male patients (mean age 30 years) who developed myocarditis after receiving either a first or second Pfizer/BioNTech vaccine, absolute LGE declined in all patients over time, and completely resolved in one person, after a median follow-up of 212 days. In addition, left ventricular ejection fraction increased in five of the seven patients and there were no adverse cardiovascular events, including hospital readmissions, arrhythmias, or mortality.  

“This is good news,” lead researcher Arthur Shiyovich, MD (Rabin Medical Center, Tel Aviv, Israel), told TCTMD. “We know from previous studies, mostly the ITAMY study, that the follow-up MRI is very important in terms of predicting long-term outcomes of these patients. Of course, we do need long-term clinical follow-up, but this follow-up cardiac MR study supports very good long-term outcomes for patients with vaccine-associated myocarditis.”

Senior investigator of the second series, Ashraf Hamdan, MD (Rabin Medical Center), agreed. “These findings support the relatively favorable clinical course and outcomes of these patients,” he said in an email.

Both studies were published last week in JACC: Cardiovascular Imaging.

Favorable Prognosis

Several case reports and case series have shown there is a small risk of myocarditis associated with the mRNA vaccines, particularly in young men, and that risk tends to be a little higher with the Moderna vaccine. Cardiac imaging suggested that these cases resembled “classical” myocarditis and tended to be relatively mild. There has been data published suggesting that myocarditis after vaccination does resolve without clinical consequences, with these studies showing increases in LVEF and resolution of LGE on cardiac MR.

The Israeli researchers previously published data documenting mostly mild myocarditis after vaccination in 54 patients. In their initial analysis, the cumulative incidence of myocarditis was low at 2.13 cases per 100,000 persons. In males ages 16 to 29 years old, the cumulative incidence was nearly 11 cases per 100,000 persons, however.

Of the 54 original patients, 15 had a cardiac MR scan performed a median 4 days after diagnosis. The follow-up study, which included seven patients undergoing MRI after a median of a little more than 7 months, showed there was a statistically significant improvement in LVEF between the two MR studies (56.8% to 59.4%; P = 0.046). LGE also declined between MR scans, with all patients showing signs of improvement or resolution.

“We still need long-term clinical follow-up,” said Shiyovich, adding the initial MR imaging data are very promising. “It will help us treat these patients, in getting them back to work and back to physical activity. We see that a great part of this damage is actually reversible. It’s improving. LGE is a marker of myocardial cell damage, but in this context it’s probably not fibrosis, it’s not scar, but rather edema. It’s reversible damage, at least partially. I think this is really great news for this new entity.” 

In the US study, the nine males were diagnosed with myocarditis after receiving the Pfizer/BioNTech (n = 7) or Moderna (n = 2) vaccine and underwent a follow-up cardiac MR scan a median 94 days after diagnosis. As noted by Patel, there was MR evidence of myocardial recovery, and no clinical events, in follow-up, but there were also signs that some mild abnormalities persisted as evidenced by measures of global longitudinal strain and global circumferential strain.

Like Shiyovich, Patel said the mRNA vaccination-related myocarditis looks very similar to classic myocarditis, with comparable LGE scar patterns.

“That’s a good thing because we can extrapolate the data from viral myocarditis to this group of patients,” he said. “Most of the patients with COVID-19 vaccination-induced myocarditis had LGE in the lateral wall of the left ventricle, and not in the septum. If it’s in the septum, it carries a worse prognosis.” Based on the data, and what’s known so far, “I feel the cases of vaccination-related myocarditis follow a benign course,” said Patel.