title: A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination.
abstract: BACKGROUND
  Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined.
  
  
  OBJECTIVE
  The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization.
  
  
  METHODS
  New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV).
  
  
  RESULTS
  New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group.
  
  
  CONCLUSIONS
  Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized.
authors: Military Vaccine Agency-Vaccine Healthcare Centers Network (currently Defense Health Agency, Immunization Healthcare Branch), Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America; Department of Medicine and Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
authors: Renata J M
authors: RJ
authors: Engler
authors: Department of Medicine and Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America; Allergy-Immunology-Immunizations, Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America.
authors: Michael R
authors: MR
authors: Nelson
authors: Military Vaccine Agency-Vaccine Healthcare Centers Network (currently Defense Health Agency, Immunization Healthcare Branch), Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America.
authors: Limone C
authors: LC
authors: Collins
authors: Military Vaccine Agency-Vaccine Healthcare Centers Network (currently Defense Health Agency, Immunization Healthcare Branch), Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America.
authors: Christina
authors: C
authors: Spooner
authors: Cardiology Service, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
authors: Brian A
authors: BA
authors: Hemann
authors: Cardiology Service, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
authors: Barnett T
authors: BT
authors: Gibbs
authors: Cardiology Service, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
authors: J Edwin
authors: JE
authors: Atwood
authors: Department of Research Programs, Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America.
authors: Robin S
authors: RS
authors: Howard
authors: Department of Research Programs, Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America.
authors: Audrey S
authors: AS
authors: Chang
authors: Department of Pathology, Vassar Brothers Medical Center, Poughkeepsie, New York, United States of America.
authors: Daniel L
authors: DL
authors: Cruser
authors: Cardiology Service, Fort Belvoir Community Hospital, Fort Belvoir, Virginia, United States of America.
authors: Daniel G
authors: DG
authors: Gates
authors: Integrated Cardiac Health Project, Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America.
authors: Marina N
authors: MN
authors: Vernalis
authors: Allergy and Asthma Care Centers, Chantilly, Virginia, United States of America.
authors: Marguerite S
authors: MS
authors: Lengkeek
authors: Military Vaccine Agency-Vaccine Healthcare Centers Network (currently Defense Health Agency, Immunization Healthcare Branch), Womack Army Medical Center, Fort Bragg, North Carolina, United States of America.
authors: Bruce M
authors: BM
authors: McClenathan
authors: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Allan S
authors: AS
authors: Jaffe
authors: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Leslie T
authors: LT
authors: Cooper
authors: Cincinnati Children's Hospital Center for Global Health, Cincinnati, Ohio, United States of America.
authors: Steve
authors: S
authors: Black
authors: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors: Christopher
authors: C
authors: Carlson
authors: Department of Immunology, University of Washington, Seattle, Washington, United States of America.
authors: Christopher
authors: C
authors: Wilson
authors: Center for Biomedical Informatics, University of Tennessee Health Sciences Center, Memphis, Tennessee, United States of America; Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States of America.
authors: Robert L
authors: RL
authors: Davis
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003710:Demography; D005260:Female; D006801:Humans; D015994:Incidence; D007252:Influenza Vaccines / Q000009:adverse effects*; D008297:Male; D009205:Myocarditis / Q000453:epidemiology*; D010493:Pericarditis / Q000453:epidemiology*; D011446:Prospective Studies; D012900:Smallpox Vaccine / Q000009:adverse effects*; D016896:Treatment Outcome; D020107:Troponin T / Q000378:metabolism; D014481:United States / Q000453:epidemiology; D014611:Vaccination / Q000009:adverse effects*; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D007252:Influenza Vaccines; D012900:Smallpox Vaccine; D020107:Troponin T; D015164:Vaccines, Inactivated