Cardiac problems still plague smallpox program

Four cases of dilated hearts under review

Public health experts continue to puzzle over the possible link between the smallpox vaccine and heart problems, as they investigate four recent cases of serious heart ailments. Meanwhile, a study of a 1947 mass smallpox vaccination in New York City lends credence to the theory that the three cardiac-related deaths that occurred after vaccination were not associated with the vaccine.

Two health care workers and two military vaccinees have developed dilated hearts, a severe cardiomyopathy that began gradually and was diagnosed three to five months after smallpox vaccination, says John Neff, MD, chair of the Smallpox Vaccine Safety Working Group of the Advisory Committee on Immunization Practices.

All four cases of dilated cardiomyopathy occurred among people who had previously been vaccinated, and all were older than their vaccination cohort. The two military men were 37 and 43 years old, while the median age for military vaccinees is 27. The two female health care workers were 53 and 55, while the median age for civilian vaccinees is 48. The women had a history of obesity and hypertension but no history of ischemic heart disease, according to a report in the Centers for Disease Control and Prevention’s Mortality and Morbidity Weekly Report (MMWR). With treatment, the women have been able to continue to work, the report said.1

"We continue to feel this is a very, very important avenue to follow [for investigation]," says Neff, who is professor of pediatrics at the University of Washington School of Medicine and director of the Center for Children with Special Needs at Children’s Hospital and Regional Medical Center in Seattle.

"These people have significant heart disease," says Raymond Strikas, MD, director of CDC’s Smallpox Preparation and Response Activity. "We don’t know if it’s related to the vaccine. We’re concerned that’s a possibility."

Among about 577,000 military vaccinees, two cases of dilated cardiomyopathy would not be above the normal, expected rate for that population, says Col. John Grabenstein, RPh, PhD, deputy director of clinical operations for the Military Vaccine Agency. The rate for unvaccinated individuals would be 1.6 per 100,000, he adds.

"At this point, our number of cases is not above what we normally see," he says, noting that the Department of Defense continues to follow up on its vaccinees.

CDC has asked clinicians to report cases of dilated cardiomyopathy among vaccinees, even if they occur months after vaccination. "Smallpox vaccination has not been associated previously with [the condition]," the MMWR report said. "Because smallpox vaccination appears to be associated causally with myocarditis, which can cause dilated cardiomyopathy, further evaluation is warranted."

Screening vaccinees for cardiac risk factors was designed to avoid ischemic events that may be related to the vaccine. But according to a study by the CDC and the New York City Department of Health, history shows that the vaccine doesn’t lead to higher rates of cardiac-related deaths.

About 6 million New Yorkers — 80% of the city’s population — received the smallpox vaccine in a four-week period in 1947 after a smallpox outbreak. Public health officers recently sorted through 81,000 death certificates in the municipal achieves, looking for variations in cardiac deaths or overall deaths during a two-week post-vaccination risk period. The 1947 strain of vaccinia was identical to the one used in the 2003 vaccine.2

"We were able to pull all of the death records for that year as well as one year before and one year after," says Melissa A. Marx, PhD, MPH, an epidemic intelligence service officer with the New York City Department of Health and the CDC. "We didn’t see any increase in cardiac-related deaths after vaccination."

Marx notes that in 1947, no one was screened for contraindications. Anyone who wanted the vaccine could get it. The population at the time also had a higher overall rate of cardiac death and more risk factors, such as smoking.

"[The study] is part of the growing body of evidence that smallpox vaccination isn’t causally related to cardiac-related deaths," she says.

Autopsies of the three vaccinees who suffered fatal heart attacks did not show any evidence of myopericarditis, which has been associated with the vaccine. However, Marx stresses that screening for cardiac risk factors should continue in the absence of any known cases of smallpox.

Will myocarditis cases recover fully?

Meanwhile, public health officials continue to track the cases of myocarditis or pericarditis, inflammation of the heart or heart lining, which they say may be linked to smallpox vaccination. Of about 500,000 military personnel vaccinated, 58 developed the condition (56 probable, two confirmed). At an eight-week follow-up of 35 cases, 28 reported complete clinical recovery, Grabenstein says. Seven had intermittent chest pain, and two of those had persistent, nonspecific ECG changes.

In the civilian program, which now has vaccinated 38,489 health care workers, public health workers, and first responders, there are 22 cases of myopericarditis (16 suspected, six probable).

Myocarditis can sometimes lead to recurrent heart problems or eventual heart failure. "We don’t know if the people with myocarditis will stay completely recovered," says Strikas. "We’re working with a group of cardiologists to see how long we need to follow up."

There is no known way to screen future vaccinees to lesson the risk of myocarditis.

"We don’t know what the predisposing factors are for people to develop myocarditis or pericarditis," he says. "It’s not clear what the risk factors are."


1. Centers for Disease Control and Prevention. Update: Cardiac and other adverse events following civilian smallpox vaccination — United States, 2003. MMWR 2003; 52:639-642.

2. Frieden T, Mostashari F, Schwartz SP. Cardiac deaths after a mass smallpox vaccination campaign — New York City, 1947. MMWR 2003; 52:933-936.