The rate of adverse cardiac events was about 58 per 100,000 vaccinations in data collected between January and May 2003, said Richard Schieber, M.D., of the Smallpox Vaccine Adverse Events Monitoring and Response Activity, National Immunization Program at the Centers for Disease Control and Prevention (CDC) in Atlanta, Ga.
Twenty-four cases of pericarditis, myocarditis, dilated cardiomyopathy or acute coronary syndromes (heart attack or chest pain known as angina) were identified among 37,876 U.S. civilian healthcare workers vaccinated as part of the nation's bioterrorism readiness program. Twenty-two patients had pericarditis or myocarditis.
Pericarditis is inflammation of the pericardium, the thin sac (membrane) that surrounds the heart and the roots of the great blood vessels. Chest pain is one of the first signs.
Myocarditis is inflammation of the heart muscle caused by conditions such as infection, rheumatic fever, diphtheria, tuberculosis or toxic drug poisoning.
The average interval from vaccination to illness was about 12 days. Most patients with myocarditis had a mild form of the disease, but two of eight patients with acute coronary syndromes died suddenly within three weeks after vaccination. Five of the eight had three or more risk factors for, or a history of, coronary artery disease before vaccination.
In a large population in the same age range, some acute coronary events will occur over several weeks even in the absence of any identifiable cause, Schieber said.
Public health officials expected some adverse reactions associated with the smallpox program, but didn't anticipate heart complications, he said.
"As the civilian vaccination program unfolded, we received reports about cardiac complications among the military personnel in December, in addition to some apparent cases of myocarditis and pericarditis," he said. "Since the deaths occurred soon after the vaccinations, the CDC convened an emergency meeting to review the data and determine if changes were needed in the vaccine program."
"While we couldn't determine a direct causal link between the vaccine and the acute coronary syndrome, the CDC did recommend that anyone who has three of these five known heart disease risk factors -- high blood pressure, high cholesterol, diabetes, a family history of heart disease or cigarette smoking -- should not be vaccinated."
John Murphy, M.D., a cardiologist at the Mayo Clinic in Rochester, Minn., studied 18 cases of myocarditis or pericarditis among 230,000 military personnel.
"That's an incidence of about one case per 12,700 vaccinees," Murphy said.
In the third study, Gregory K. Bruce, M.D., reported biopsy results from one of those 18 cases. The 29-year-old soldier was admitted to the hospital with shortness of breath two weeks after he received his smallpox vaccination. He also had elevated cardiac troponin levels, which indicates heart muscle damage, and high C-reactive protein levels, which indicates inflammation.
Myocarditis was confirmed with a biopsy. After he was diagnosed, further tests suggested that his heart muscle injury was caused by an immune system response to the initial vaccination.
"The smallpox vaccine appears to be associated with myocarditis and pericarditis, but so far disease has been mild in civilians who received the vaccine," Schieber said.
The relationship between the vaccine and acute coronary syndromes or heart attacks is still not clear, he said.
In a statement regarding the first ischemic heart disease complications that occurred after vaccinations began, the American Heart Association said, "In the past, cardiac complications after smallpox vaccination have been rare, but the majority of individuals undergoing vaccination in previous programs were children or young adults at low risk for underlying heart disease. Now that a large number of adults are receiving the vaccine, especially those in middle age who may have underlying heart disease, it will be important to carefully and continuously monitor the situation."
The American Heart Association urges people who have been vaccinated for smallpox to be aware of the symptoms of pericarditis, myocarditis and acute coronary syndromes and to contact their healthcare provider with any concern about their heart health. These symptoms may include chest pain or discomfort, palpitations, shortness of breath, ankle swelling, and/or unusual fatigue.
Schieber's co-authors are Juliett Morgan; Martha H. Roper; Linda Neff; Louisa Chapman; John Iskander; Gina Mootry; Laurence Sperling; Rose Marie Robertson and David Swerdlow.
Murphy and Bruce's co-authors are Scott Wright; Keith Bruce; James Riddle; William D. Edwards; Larry M. Baddour and Leslie T. Cooper.
NR03 – 1145 (SS03/Schieber/Smallpox)
P3391 (11/11/03 9:30 a.m.) Schieber
1825 (11/10/03 9:15 a.m.) Bruce
2358 (11/11/03 8:30 a.m.) Murphy
This news release contains updated data from the abstracts.