Search Menu
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information
Search Scholarly Publications

Title: A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination

Journal Article · · PLoS ONE
 [1];  [2];  [3];  [3];  [2];  [2];  [2];  [3];  [3];  [4];  [5];  [3];  [6];  [7];  [8];  [8];  [9];  [10];  [11];  [12] more »;  [13] « less
  1. Uniformed Services Univ. of the Health Sciences, Bethesda, MD (United States)
  2. Uniformed Services Univ. of the Health Sciences, Bethesda, MD (United States); Walter Reed National Military Medical Center, Bethesda, MD (United States)
  3. Walter Reed National Military Medical Center, Bethesda, MD (United States)
  4. Vassar Brothers Medical Center, Poughkeepsie, NY (United States)
  5. Fort Belvoir Community Hospital, Fort Belvoir, VA (United States)
  6. Allergy and Asthma Care Centers, Chantilly, VA (United States)
  7. Womack Army Medical Center, Fort Bragg, NC (United States)
  8. Mayo Clinic, Rochester, MN (United States)
  9. Cincinnati Children's Hospital Center for Global Health, Cincinnati, OH (United States)
  10. Fred Hutchinson Cancer Research Center, Seattle, WA (United States)
  11. Bill and Melinda Gates Foundation, Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States)
  12. Univ. of Tennessee Health Sciences Center, Memphis, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  13. Univ. of British Columbia, Vancouver, BC (Canada)
+ Show Author Affiliations

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. 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. 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. In conclusion, 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.

Research Organization:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC05-00OR22725
OSTI ID:
1333076
Journal Information:
PLoS ONE, Vol. 10, Issue 3; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

References (71)

Electrocardiography Screening for Cardiotoxicity after Modified Vaccinia Ankara Vaccination journal January 2009
US military service members vaccinated against smallpox in 2003 and 2004 experience a slightly higher risk of hospitalization postvaccination journal July 2008
Genetic Basis for Adverse Events after Smallpox Vaccination journal July 2008
Highly sensitive cardiac troponin T and long-term mortality in a population of community-derived perimenopausal women: nested case-control study journal January 2013
The kinetics of highly sensitive cardiac troponin T release after prolonged treadmill exercise in adolescent and adult athletes journal August 2012
Cardiac Troponin T: A Marker in the Diagnosis of Acute Myocarditis in Children journal November 2004
Detection of acute changes in circulating troponin in the setting of transient stress test-induced myocardial ischaemia using an ultrasensitive assay: results from TIMI 35 journal May 2008
Kinetics of Serum Cytokines after Primary or Repeat Vaccination with the Smallpox Vaccine journal April 2010
Integrated analysis of genetic and proteomic data identifies biomarkers associated with adverse events following smallpox vaccination journal October 2008
Consequences of unlocking the cardiac myosin molecule in human myocarditis and cardiomyopathies journal January 2008
Critical Cytokine Pathways to Cardiac Inflammation journal October 2011
Elevated baseline hs-cTnT levels predict exercise-induced myocardial ischemia in patients with peripheral arterial disease journal October 2012
Evaluation of 21st-Century Risks of Smallpox Vaccination and Policy Options journal March 2003
Cardiac Troponin T in Patients With Clinically Suspected Myocarditis journal November 1997
Smallpox vaccination and ischemic coronary events in healthy adults journal December 2007
Exercise-Induced Troponin Elevation journal December 2010
Symptomatic Pericarditis After Influenza Vaccination journal June 2000
Understanding vaccine safety information from the Vaccine Adverse Event Reporting System journal January 2004
Recommendations for the use of cardiac troponin measurement in acute cardiac care journal August 2010
The incidence and epidemiology of myocarditis journal August 1999
Exercise-Induced Cardiac Troponin Elevation journal July 2010
Changes to the cardiac biomarkers of non-elite athletes completing the 2009 London Marathon journal March 2013
Etiology of Mild Acute Infectious Myocarditis: Relation to Clinical Features journal January 1983
Comparison of military and civilian reporting rates for smallpox vaccine adverse events journal January 2007
Association of Troponin T Detected With a Highly Sensitive Assay and Cardiac Structure and Mortality Risk in the General Population journal December 2010
Increasingly Sensitive Assays for Cardiac Troponins: A Review journal June 2013
Prospective Surveillance for Cardiac Adverse Events in Healthy Adults Receiving Modified Vaccinia Ankara Vaccines: A Systematic Review journal January 2013
Myopericarditis following Smallpox Vaccination journal October 2004
Plasma 99th Percentile Reference Limits for Cardiac Troponin and Creatine Kinase MB Mass for Use with European Society of Cardiology/American College of Cardiology Consensus Recommendations journal August 2003
Minor elevations in troponin T values enhance risk assessment in emergency department patients with suspected myocardial ischemia: analysis of novel troponin T cut-off values journal May 2004
Follow‐Up of Cardiovascular Adverse Events after Smallpox Vaccination among Civilians in the United States, 2003 journal March 2008
Troponin T, B-type natriuretic peptide, C-reactive protein, and cause-specific mortality journal February 2013
Guillain–Barré syndrome coexisting with pericarditis or nephrotic syndrome after influenza vaccination journal March 2004
Physical Activity, Change in Biomarkers of Myocardial Stress and Injury, and Subsequent Heart Failure Risk in Older Adults journal December 2012
Myocarditis, Pericarditis, and Dilated Cardiomyopathy after Smallpox Vaccination among Civilians in the United States, January–October 2003 journal March 2008
Increased circulating High-Sensitivity Troponin T concentrations in children and adolescents with obesity and the metabolic syndrome: A marker for early cardiac damage? journal April 2013
Marathon Running as a Cause of Troponin Elevation: A Systematic Review and Meta-Analysis: CAUSE OF TROPONIN ELEVATION journal July 2010
Immune Effector Mechanisms Implicated in Atherosclerosis: From Mice to Humans journal June 2013
Safety Profile of Smallpox Vaccine: Insights from the Laboratory Worker Smallpox Vaccination Program journal April 2005
Adverse Reactions to Smallpox Vaccine: The Israel Defense Force Experience, 1991 to 1996. A Comparison with Previous Surveys journal April 2000
Immune Effector Mechanisms Implicated in Atherosclerosis: From Mice to Humans journal August 2013
Increasingly Sensitive Assays for Cardiac Troponins: A Review journal June 2013
Comparison of military and civilian reporting rates for smallpox vaccine adverse events journal January 2007
Troponin T, B-type natriuretic peptide, C-reactive protein, and cause-specific mortality journal February 2013
Minor elevations in troponin T values enhance risk assessment in emergency department patients with suspected myocardial ischemia: analysis of novel troponin T cut-off values journal May 2004
Guillain–Barré syndrome coexisting with pericarditis or nephrotic syndrome after influenza vaccination journal March 2004
Immune Effector Mechanisms Implicated in Atherosclerosis: From Mice to Humans journal August 2013
AHA/ACCF/HRS Recommendations for the Standardization and Interpretation of the Electrocardiogram journal March 2009
Exercise-Induced Cardiac Troponin Elevation journal July 2010
Increased circulating High-Sensitivity Troponin T concentrations in children and adolescents with obesity and the metabolic syndrome: A marker for early cardiac damage? journal April 2013
US military service members vaccinated against smallpox in 2003 and 2004 experience a slightly higher risk of hospitalization postvaccination journal July 2008
Myocarditis journal February 2012
Integrated analysis of genetic and proteomic data identifies biomarkers associated with adverse events following smallpox vaccination journal October 2008
Incidence of three presentations of acute myocarditis in young men in military service. A 20-year experience journal August 1999
Safety Profile of Smallpox Vaccine: Insights from the Laboratory Worker Smallpox Vaccination Program journal April 2005
Follow‐Up of Cardiovascular Adverse Events after Smallpox Vaccination among Civilians in the United States, 2003 journal March 2008
Myocarditis, Pericarditis, and Dilated Cardiomyopathy after Smallpox Vaccination among Civilians in the United States, January–October 2003 journal March 2008
Kinetics of Serum Cytokines after Primary or Repeat Vaccination with the Smallpox Vaccine journal April 2010
Critical Cytokine Pathways to Cardiac Inflammation journal October 2011
Myopericarditis following Smallpox Vaccination journal October 2004
Detection of acute changes in circulating troponin in the setting of transient stress test-induced myocardial ischaemia using an ultrasensitive assay: results from TIMI 35 journal May 2008
Recommendations for the use of cardiac troponin measurement in acute cardiac care journal August 2010
Adverse Reactions to Smallpox Vaccine: The Israel Defense Force Experience, 1991 to 1996. A Comparison with Previous Surveys journal April 2000
Understanding vaccine safety information from the Vaccine Adverse Event Reporting System journal January 2004
Elevated cardiac troponin is an independent risk factor for short- and long-term mortality in medical intensive care unit patients journal January 2008
ECG-Changes without Subjective Symptoms after Smallpox Vaccination of Military Personnel journal April 2009
Etiology of Mild Acute Infectious Myocarditis: Relation to Clinical Features journal January 1983
Changes to the cardiac biomarkers of non-elite athletes completing the 2009 London Marathon journal March 2013
Highly sensitive cardiac troponin T and long-term mortality in a population of community-derived perimenopausal women: nested case-control study journal January 2013
Prevalence and Determinants of Troponin T Elevation in the General Population journal April 2006
ACAM2000™: The new smallpox vaccine for United States Strategic National Stockpile journal May 2010

Cited By (18)

Vaccination and risk of lone atrial fibrillation in the active component United States military journal December 2018
Estimating the Size of the U.S. Population at Risk of Severe Adverse Events from Replicating Smallpox Vaccine journal October 2016
A Holistic Assessment of the Risks and Benefits of the Synthesis of Horsepox Virus journal March 2018
Recognition and Initial Management of Fulminant Myocarditis: A Scientific Statement From the American Heart Association journal February 2020
Myocarditis journal February 2016
Inflammatory Cardiomyopathic Syndromes journal September 2017
Autoimmune/inflammatory syndrome induced by adjuvants (Shoenfeld’s syndrome) – An update journal November 2016
Clinical, serological and echocardiographic examination of healthy field dogs before and after vaccination with a commercial tetravalent leptospirosis vaccine journal May 2017
Recurrence of pericarditis after influenza vaccination: a case report and review of the literature journal May 2018
Effect of Melittin on Metabolomic Profile and Cytokine Production in PMA-Differentiated THP-1 Cells journal October 2018
Acute fulminant myocarditis following influenza vaccination requiring extracorporeal membrane oxygenation journal May 2019
Clinical, serological and echocardiographic examination of healthy field dogs before and after vaccination with a commercial tetravalent leptospirosis vaccine text January 2017
A Holistic Assessment of the Risks and Benefits of the Synthesis of Horsepox Virus journal March 2018
Recurrence of pericarditis after influenza vaccination: a case report and review of the literature journal May 2018
Immunogenicity and safety of three consecutive production lots of the non replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled phase III trial journal April 2018
The Prevalence and Findings of Subclinical Influenza-associated Cardiac Abnormalities among Japanese Patients journal July 2018
Effect of Melittin on Metabolomic Profile and Cytokine Production in PMA-Differentiated THP-1 Cells journal October 2018
Acute fulminant myocarditis following influenza vaccination requiring extracorporeal membrane oxygenation journal May 2019

Figures / Tables (8)

Table 1(p. 5)table Table 1
Table 2(p. 5)table Table 2
Table 3(p. 6)table Table 3
Fig 1(p. 7)figure Fig 1
Table 4(p. 8)table Table 4
Table 5(p. 9)table Table 5
Table 6(p. 10)table Table 6
Table 7(p. 11)table Table 7

Similar Records

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
vaccines
myocarditis
electrocardiography
smallpox
troponin
adverse events
influenza
vaccination and immunization