BACKGROUND: Symptomatic myopericarditis has been described after smallpox vaccination using replication-competent vaccinia strains. METHODS: We examined the incidence of new electrocardiogram (ECG) abnormalities and evaluated the safety and immunogenicity related to vaccination. Volunteer subjects (n=90) aged 18 to 32 years were enrolled in a National Institutes of Health-sponsored phase I smallpox vaccination trial (Division of Microbiology and Infectious Diseases 02-017) and observed over a 26-week period after 2 injections of IMVAMUNE, Modified Vaccinia Ankara vaccine (Bavarian Nordic A/S, Copenhagen, DK), followed by scarification with Dryvax (Wyeth Laboratories, Marietta, Penn). Diagnostic computer-derived ECG statements were available to the clinical study team and compared with those of a board-certified cardiologist who independently read the ECG tracings. RESULTS: Serial ECG tracings available for 89 of the subjects revealed new ST-segment abnormalities in 2.2% and new T-wave abnormalities in 15.7%; the majority (71.4%) resolved on subsequent tracings. Cardiologist over-read of computer statements resulted in frequent changes in readings, particularly negation of cardiac arrhythmias. A cardiology consultation was requested in 17 subjects for nonspecific cardiac symptoms or new abnormal ECG findings. Echocardiograms were performed in 12 of the 17 subjects and were normal except for 1 subject with possible myopericarditis after receiving Dryvax. CONCLUSION: New minor ECG abnormalities are common in apparently young healthy volunteers considered for smallpox vaccination trials. Cardiologist over-read of computer-generated ECG statements in vaccine trials using ECG as a screening tool for safety can reduce false-positive computer-determined ECG diagnoses and the need for inappropriate cardiology referral and additional noninvasive testing.
RCT Entities:
BACKGROUND: Symptomatic myopericarditis has been described after smallpox vaccination using replication-competent vaccinia strains. METHODS: We examined the incidence of new electrocardiogram (ECG) abnormalities and evaluated the safety and immunogenicity related to vaccination. Volunteer subjects (n=90) aged 18 to 32 years were enrolled in a National Institutes of Health-sponsored phase I smallpox vaccination trial (Division of Microbiology and Infectious Diseases 02-017) and observed over a 26-week period after 2 injections of IMVAMUNE, Modified Vaccinia Ankara vaccine (Bavarian Nordic A/S, Copenhagen, DK), followed by scarification with Dryvax (Wyeth Laboratories, Marietta, Penn). Diagnostic computer-derived ECG statements were available to the clinical study team and compared with those of a board-certified cardiologist who independently read the ECG tracings. RESULTS: Serial ECG tracings available for 89 of the subjects revealed new ST-segment abnormalities in 2.2% and new T-wave abnormalities in 15.7%; the majority (71.4%) resolved on subsequent tracings. Cardiologist over-read of computer statements resulted in frequent changes in readings, particularly negation of cardiac arrhythmias. A cardiology consultation was requested in 17 subjects for nonspecific cardiac symptoms or new abnormal ECG findings. Echocardiograms were performed in 12 of the 17 subjects and were normal except for 1 subject with possible myopericarditis after receiving Dryvax. CONCLUSION: New minorECG abnormalities are common in apparently young healthy volunteers considered for smallpox vaccination trials. Cardiologist over-read of computer-generated ECG statements in vaccine trials using ECG as a screening tool for safety can reduce false-positive computer-determined ECG diagnoses and the need for inappropriate cardiology referral and additional noninvasive testing.
Authors: Robert E Eckart; Suzanne S Love; J Edwin Atwood; Mark K Arness; Dimitri C Cassimatis; Charles L Campbell; Sheri Y Boyd; Joseph G Murphy; David L Swerdlow; Limone C Collins; James R Riddle; David N Tornberg; John D Grabenstein; Renata J M Engler Journal: J Am Coll Cardiol Date: 2004-07-07 Impact factor: 24.094
Authors: Richard N Greenberg; Edgar Turner Overton; David W Haas; Ian Frank; Mitchell Goldman; Alfred von Krempelhuber; Garth Virgin; Nicole Bädeker; Jens Vollmar; Paul Chaplin Journal: J Infect Dis Date: 2012-12-07 Impact factor: 5.226
Authors: Renata J M Engler; Michael R Nelson; Limone C Collins; Christina Spooner; Brian A Hemann; Barnett T Gibbs; J Edwin Atwood; Robin S Howard; Audrey S Chang; Daniel L Cruser; Daniel G Gates; Marina N Vernalis; Marguerite S Lengkeek; Bruce M McClenathan; Allan S Jaffe; Leslie T Cooper; Steve Black; Christopher Carlson; Christopher Wilson; Robert L Davis Journal: PLoS One Date: 2015-03-20 Impact factor: 3.240
Authors: Eva-Maria Zitzmann-Roth; Frank von Sonnenburg; Stephan de la Motte; Nathaly Arndtz-Wiedemann; Alfred von Krempelhuber; Nadine Uebler; Jens Vollmar; Garth Virgin; Paul Chaplin Journal: PLoS One Date: 2015-04-16 Impact factor: 3.240
Authors: Marnie L Elizaga; Sandhya Vasan; Mary A Marovich; Alicia H Sato; Dale N Lawrence; Bernard R Chaitman; Sharon E Frey; Michael C Keefer Journal: PLoS One Date: 2013-01-17 Impact factor: 3.240