Carotid artery examination, an important tool in patient evaluation.

Examination of the arteries is an age old medical tradition. Examination of the carotid artery is of unique importance because it is an easily accessible large artery. Through the methods of inspection, palpation, and auscultation, carotid artery examination gives clinicians important diagnostic clues about the health and disease of the patient. Inspection and palpation of the carotid give insight into left ventricular systolic function and distinguish types of valvular heart disease. Auscultation identifies patients with high-risk atherosclerosis. In most cases carotid examination is neither sensitive nor specific, but in the correct clinical context it offers important evidence leading to specific diagnoses and treatment. In this review, we discuss the examination of the carotid artery under normal conditions and describe how abnormalities in the carotid artery examination are indicators of disease.

Carotid bruits and cerebrovascular disease risk: a meta-analysis.

BACKGROUND AND PURPOSE: Current guidelines recommend against routine auscultation of carotid arteries, believing that carotid bruits are poor predictors of either underlying carotid stenosis or stroke risk in asymptomatic patients. We investigated whether the presence of a carotid bruit is associated with increased risk for transient ischemic attack, stroke, or death by stroke (stroke death). METHODS: We searched Medline (1966 to December 2009) and EMBASE (1974 to December 2009) with the terms "carotid" and "bruit." Bibliographies of all retrieved articles were also searched. Articles were included if they prospectively reported the incidence of transient ischemic attack, stroke, or stroke death in asymptomatic adults. Two authors independently reviewed and extracted data. RESULTS: We included 28 prospective cohort articles that followed a total of 17 913 patients for 67 708 patient-years. Among studies that directly compared patients with and without bruits, the rate ratio for transient ischemic attack was 4.00 (95% CI, 1.8 to 9.0, P<0.0005, n=5 studies), stroke was 2.5 (95% CI, 1.8 to 3.5, P<0.0005, n=6 studies), and stroke death was 2.7 (95% CI, 1.33 to 5.53, P=0.002, n=3 studies). Among the larger pool of studies that provided data on rates, transient ischemic attack rates were 2.6 per 100 patient-years (95% CI, 2.0 to 3.2, P<0.0005, n=24 studies) for those with bruits compared with 0.9 per 100 patient-years (95% CI, 0.2 to 1.6, P=0.02, n=5 studies) for those without carotid bruits. Stroke rates were 1.6 per 100 patient-years (95% CI, 1.3 to 1.9, P<0.0005, n=26 studies) for those with bruits compared with 1.3 per 100 patient-years (95% CI, 0.8 to 1.7, P<0.0005, n=6) without carotid bruits, and death rates were 0.32 (95% CI, 0.20 to 0.44, P<0.005, n=13 studies) for those with bruits compared with 0.35 (95% CI, 0.00 to 0.81, P=0.17, n=3 studies) for those without carotid bruits. CONCLUSIONS: The presence of a carotid bruit may increase the risk of cerebrovascular disease.

Carotid bruits as a prognostic indicator of cardiovascular death and myocardial infarction: a meta-analysis.

BACKGROUND: Although carotid bruits are deemed to be markers of generalised atherosclerosis, they are poor predictors of cerebrovascular events. We investigated whether a carotid bruit predicts myocardial infarction and cardiovascular death. METHODS: In this meta-analysis, we searched Medline (1966 to August, 2007) and Embase (1974 to August, 2007) with the terms "carotid" and "bruit". Bibliographies of all the retrieved articles were also searched. Articles were included if they reported the incidence of myocardial infarction or cardiovascular death in adults. Outcome variables were extracted in duplicate and included the rate of myocardial infarction and cardiovascular mortality. Quality of the articles was independently assessed with the Hayden rating scheme. Data were pooled with a random effects model. FINDINGS: Of the 22 articles included, 20 (91%) used prospective cohorts. Our analysis included 17,295 patients with 62 413.5 patient-years of follow-up, with a median sample size of 273 patients (range 38-4736) followed up for 4 years (2-7). The rate of myocardial infarction in patients with carotid bruits was 3.69 (95% CI 2.97-5.40) per 100 patient-years (eight studies) compared with 1.86 (0.24-3.48) per 100 patient-years in those without bruits (two studies). Yearly rates of cardiovascular death were also higher in patients with bruits (16 studies) than in those without (four studies) (2.85 [2.16-3.54] per 100 patient-years vs 1.11 [0.45-1.76] per 100 patient-years). In the four trials in which direct comparisons of patients with and without bruits were possible, the odds ratio for myocardial infarction was 2.15 (1.67-2.78) and for cardiovascular death 2.27 (1.49-3.49). INTERPRETATION: Auscultation for carotid bruits in patients at risk for heart disease could help select those who might benefit the most from an aggressive modification strategy for cardiovascular risk.

Amiodarone versus sotalol for atrial fibrillation.

BACKGROUND: The optimal pharmacologic means to restore and maintain sinus rhythm in patients with atrial fibrillation remains controversial. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 665 patients who were receiving anticoagulants and had persistent atrial fibrillation to receive amiodarone (267 patients), sotalol (261 patients), or placebo (137 patients) and monitored them for 1 to 4.5 years. The primary end point was the time to recurrence of atrial fibrillation beginning on day 28, determined by means of weekly transtelephonic monitoring. RESULTS: Spontaneous conversion occurred in 27.1 percent of the amiodarone group, 24.2 percent of the sotalol group, and 0.8 percent of the placebo group, and direct-current cardioversion failed in 27.7 percent, 26.5 percent, and 32.1 percent, respectively. The median times to a recurrence of atrial fibrillation were 487 days in the amiodarone group, 74 days in the sotalol group, and 6 days in the placebo group according to intention to treat and 809, 209, and 13 days, respectively, according to treatment received. Amiodarone was superior to sotalol (P<0.001) and to placebo (P<0.001), and sotalol was superior to placebo (P<0.001). In patients with ischemic heart disease, the median time to a recurrence of atrial fibrillation was 569 days with amiodarone therapy and 428 days with sotalol therapy (P=0.53). Restoration and maintenance of sinus rhythm significantly improved the quality of life and exercise capacity. There were no significant differences in major adverse events among the three groups. CONCLUSIONS: Amiodarone and sotalol are equally efficacious in converting atrial fibrillation to sinus rhythm. Amiodarone is superior for maintaining sinus rhythm, but both drugs have similar efficacy in patients with ischemic heart disease. Sustained sinus rhythm is associated with an improved quality of life and improved exercise performance.

Exercise capacity and mortality among men referred for exercise testing.

BACKGROUND: Exercise capacity is known to be an important prognostic factor in patients with cardiovascular disease, but it is uncertain whether it predicts mortality equally well among healthy persons. There is also uncertainty regarding the predictive power of exercise capacity relative to other clinical and exercise-test variables. METHODS: We studied a total of 6213 consecutive men referred for treadmill exercise testing for clinical reasons during a mean (+/-SD) of 6.2+/-3.7 years of follow-up. Subjects were classified into two groups: 3679 had an abnormal exercise-test result or a history of cardiovascular disease, or both, and 2534 had a normal exercise-test result and no history of cardiovascular disease. Overall mortality was the end point. RESULTS: There were a total of 1256 deaths during the follow-up period, resulting in an average annual mortality of 2.6 percent. Men who died were older than those who survived and had a lower maximal heart rate, lower maximal systolic and diastolic blood pressure, and lower exercise capacity. After adjustment for age, the peak exercise capacity measured in metabolic equivalents (MET) was the strongest predictor of the risk of death among both normal subjects and those with cardiovascular disease. Absolute peak exercise capacity was a stronger predictor of the risk of death than the percentage of the age-predicted value achieved, and there was no interaction between the use or nonuse of beta-blockade and the predictive power of exercise capacity. Each 1-MET increase in exercise capacity conferred a 12 percent improvement in survival. CONCLUSIONS: Exercise capacity is a more powerful predictor of mortality among men than other established risk factors for cardiovascular disease.

Exercise capacity in atrial fibrillation: a substudy of the Sotalol-Amiodarone Atrial Fibrillation Efficacy Trial (SAFE-T).

BACKGROUND: Therapy for chronic atrial fibrillation (AF) focuses on rate versus rhythm control, but little is known about the effects of common therapeutic interventions on exercise tolerance in AF. METHODS: Six hundred fifty-five patients with chronic AF underwent maximal exercise testing at baseline and 8 weeks, 6 months, and 1 year after randomization to sotalol, amiodarone, or placebo therapy and attempted direct current cardioversion. Analyses of baseline determinants of exercise capacity, predictors of change in exercise capacity at 6 months and 1 year, and the short- and long-term effects of cardioversion on exercise capacity were made. RESULTS: Age, obesity, and presence of symptoms accompanying AF were inversely associated with baseline exercise capacity, but these factors accounted for only 10% of the variance in exercise capacity. Patients most likely to benefit from cardioversion were those most limited initially, younger, not obese or hypertensive, and with an uncontrolled ventricular rate at baseline. Conversion to sinus rhythm (SR) resulted in significant reductions in resting (approximately 25 beat/min) and peak exercise (approximately 40 beat/min) heart rates at 6 months and 1 year (P < .001). Successful cardioversion improved exercise capacity by 15% at 8 weeks, and these improvements were maintained throughout the year. This improvement was observed both among those who maintained SR and those with intermittent AF. CONCLUSION: Cardioversion resulted in a sustained improvement in exercise capacity over the course of 1 year, and this improvement was similar between those in SR and those with SR and recurrent AF. Patients most likely to improve with treatment tended to be younger and nonobese and have the greatest limitations initially.

Peripheral edema due to heart disease: diagnosis and outcome.

BACKGROUND: The purpose of this study was to determine whether baseline physical examination and history are useful in identifying patients with cardiac edema as defined by echocardiography, and to compare survival for patients with cardiac and noncardiac causes of edema. HYPOTHESIS: Physical examination and history data can help to identify patients with edema who have significant cardiac disease. METHODS: We reviewed the medical records of 278 consecutive patients undergoing echocardiography for evaluation of peripheral edema. We classified cardiac edema as the presence of any of the following: left ventricular ejection fraction < 45%, systolic pulmonary artery pressure > 45 mmHg, reduced right ventricular function, enlarged right ventricle, and a dilated inferior vena cava. RESULTS: The mean age of the 243 included patients was 67 +/- 12 years and 92% were male. A cardiac cause of edema was found in 56 (23%). Independent predictors of a cardiac cause of edema included chronic obstructive pulmonary disease (COPD, odds ratio [OR] 1.74, 95% confidence interval [CI] 1.14-2.60) and crackles (OR 1.98, 95% CI 1.26-3.10). The specificity for a cardiac cause of edema was high (91% for COPD, 93% for crackles); however, the sensitivity was quite low (27% for COPD, for 24% crackles). Compared with patients without a cardiac cause of edema, those with a cardiac cause had increased mortality (25 vs. 8% at 2 years, p < 0.01), even after adjustment for other characteristics (hazard ratio 1.55, 95% CI 1.08-2.24). CONCLUSIONS: A cardiac cause of edema is difficult to predict based on history and examination and is associated with high mortality.

Smallpox vaccination and myopericarditis: a clinical review.

Smallpox is a devastating viral illness that was eradicated after an aggressive, widespread vaccination campaign. Routine U.S. childhood vaccinations ended in 1972, and routine military vaccinations ended in 1990. Recently, the threat of bioterrorist use of smallpox has revived the need for vaccination. Over 450,000 U.S. military personnel received the vaccination between December 2002 and June 2003, with rates of non-cardiac complications at or below historical levels. The rate of cardiac complications, however, has been higher than expected, with two confirmed cases and over 50 probable cases of myopericarditis after vaccination reported to the Department of Defense Smallpox Vaccination Program. The practicing physician should use the history and physical, electrocardiogram, and cardiac biomarkers in the initial evaluation of a post-vaccination patient with chest pain. Echocardiogram, cardiac catheterization, magnetic resonance imaging, nuclear imaging, and cardiac biopsy may be of use in further workup. Treatment is with non-steroidal anti-inflammatory agents, four to six weeks of limited exertion, and conventional heart failure treatment as necessary. Immune suppressant therapy with steroids may be uniquely beneficial in myopericarditis related to smallpox vaccination, compared with other types of myopericarditis. If a widespread vaccination program is undertaken in the future, many more cases of post-vaccinial myopericarditis could be seen. Practicing physicians should be aware that smallpox vaccine-associated myopericarditis is a real entity, and symptoms after vaccination should be appropriately evaluated, treated if necessary, and reported to the Vaccine Adverse Events Reporting System.

Incidence and follow-up of inflammatory cardiac complications after smallpox vaccination.

OBJECTIVES: The purpose of this study was to assess the follow-up of patients with vaccinia-associated myocarditis. BACKGROUND: With the threat of biological warfare, the U.S. Department of Defense resumed a program for widespread smallpox vaccinations on December 13, 2002. One-year afterwards, there has been a significant increase in the occurrence of myocarditis and pericarditis among those vaccinated. METHODS: Cases were identified through sentinel reporting to military headquarters, systematic surveillance, and spontaneous reports. RESULTS: A total of 540,824 military personnel were vaccinated with a New York City Board of Health strain of vaccinia from December 2002 through December 2003. Of these, 67 developed myopericarditis at 10.4 +/- 3.6 days after vaccination. The ST-segment elevation was noted in 57%, mean troponin on admission was 11.3+/- 22.7 ng/dl, and peak cardiac enzymes were noted within 8 h of presentation. On follow-up of 64 patients (96%) at a mean of 32 +/- 16 weeks, all patients had objective normalization of echocardiography, electrocardiography, laboratory testing, graded exercise testing, and functional status; 8 (13%) reported atypical, non-limiting persistent chest discomfort. CONCLUSIONS: Post-vaccinial myopericarditis should be considered in patients with chest pain within 30 days after smallpox vaccination. Normalization of echocardiography, electrocardiography, and treadmill testing is expected, and nearly all patients have resolution of chest pain on follow-up.

Relation of QTc duration heterogeneity to mortality following orthotopic heart transplantation.

Studies of heart failure patients have demonstrated that serial QT prolongation and abnormally prolonged QT intervals are associated with greater mortality. Serial QT interval measurements in patients who undergo orthotopic heart transplantation (OHT) may quantify the degree of myocardial repolarization heterogeneity and serve as a marker of arrhythmogenic substrate. In this study, the mean survival for those with "stable" QT(c) intervals (a change of -10 to 10 ms/year) was 124 +/- 8 months versus 63 +/- 25 months in those with annual QT(c) changes of >10 ms (p = 0.009). Ventricular repolarization heterogeneity may serve as a marker of identifying high-risk patients after OHT.

Comparison of clinical presentation of acute myocarditis following smallpox vaccination to acute coronary syndromes in patients <40 years of age.

Smallpox vaccine-associated myopericarditis may have a similar presentation to acute coronary syndrome (ACS). The clinical records of 78 young patients (<40 years of age) presenting with ACS (n = 16) or myocarditis after smallpox vaccination (n = 62) were reviewed. Comparisons were made among clinical presentation, cardiac enzymes, echocardiographic findings, and electrocardiographic changes. The presence of cardiac risk factors or focal wall motion abnormalities on echocardiography were associated with a diagnosis of ACS. There was a trend toward earlier elevation of troponin-I and creatine kinase in patients with myocarditis compared with ACS.

Exercise testing in Wolff-Parkinson-White syndrome: case report with ECG and literature review.

ECG changes during exercise stress testing, such as false-positive ST-segment depression and disappearance of the delta wave, are reported in patients with the Wolff-Parkinson-White (WPW) pattern. We present a case of exercise testing in a 53-year-old man with WPW syndrome with ischemic-appearing ECG changes and normal nuclear stress perfusion study findings who was thought to be at clinically low risk for having significant coronary disease. A literature review is discussed. Although ST-segment depression typical for ischemia occurs in half of the patients in whom WPW syndrome is reported, exercise testing is still an important tool in their evaluation. Data other than ECG response can be interpreted in the context of clinical history and physical examination findings to stratify the risk of coronary disease. Complete and sudden disappearance of the delta wave has been seen during exercise in 20% of patients with WPW syndrome and can identify those who are at low risk for sudden arrhythmic death.

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

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. PURPOSE: 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.

Peripheral edema.

Peripheral edema often poses a dilemma for the clinician because it is a nonspecific finding common to a host of diseases ranging from the benign to the potentially life threatening. A rational and systematic approach to the patient with edema allows for prompt and cost-effective diagnosis and treatment. This article reviews the pathophysiologic basis of edema formation as a foundation for understanding the mechanisms of edema formation in specific disease states, as well as the implications for treatment. Specific etiologies are reviewed to compare the diseases that manifest this common physical sign. Finally, we review the clinical approach to diagnosis and treatment strategies.

Comparison of sotalol versus amiodarone in maintaining stability of sinus rhythm in patients with atrial fibrillation (Sotalol-Amiodarone Fibrillation Efficacy Trial [Safe-T]).

The Sotalol-Amiodarone Fibrillation Efficacy Trial (SAFE-T) is a randomized, double-blind, multicenter, placebo-controlled trial in which the effects of sotalol and amiodarone in maintaining stability of sinus rhythm are being examined in patients with persistent atrial fibrillation at 20 Veterans Affairs medical centers. The time to the occurrence of atrial fibrillation or flutter in patients with atrial fibrillation converted to sinus rhythm is the primary outcome measure, with a number of parameters as secondary end points. SAFE-T had randomized 665 patients when enrollment terminated on October 31, 2001. Follow-up of patients continued until October 31, 2002, for a maximum period of 54 months and a minimum period of 12 months for all patients.

Chronotropic incompetence in a young adult: case report and literature review.

Chronotropic incompetence (CI) is the inability of heart rate response to meet metabolic demand. CI is associated with sinus node dysfunction, atrial fibrillation, or structural heart disease, and can lead to functional impairment. We report the case of a 34-year-old man with CI secondary to sinus node dysfunction who demonstrated significant improvement in functional capacity with rate-responsive pacing. Therapy for CI should be guided by the treatment of the underlying cause with consideration for rate-responsive pacing in symptomatic patients. The prognosis of CI is variable and dependent on underlying etiology.

A systolic murmur is a common presentation of aortic regurgitation detected by echocardiography.

BACKGROUND: The finding of aortic regurgitation at a classical examination is a diastolic murmur. HYPOTHESIS: Aortic regurgitation is more likely to be associated with a systolic than with a diastolic murmur during routine screening by a noncardiologist physician. METHODS: In all, 243 asymptomatic patients (mean age 42 +/- 10 years) with no known cardiac disease but at risk for aortic valve disease due to prior mediastinal irradiation (> or = 35 Gy) underwent auscultation by a noncardiologist followed by echocardiography. A systolic murmur was considered benign if it was grade < or = II/VI, not holosystolic, was not heard at the apex, did not radiate to the carotids, and was not associated with a diastolic murmur. RESULTS: Of the patients included, 122 (49%) were male, and 86 (35%) had aortic regurgitation, which was trace in 20 (8%), mild in 52 (21%), and moderate in 14 (6%). A systolic murmur was common in patients with aortic regurgitation, occurring in 12 (86%) with moderate, 26 (50%) with mild, 6 (30%) with trace, and 27 (17%) with no aortic regurgitation (p < 0.0001). The systolic murmurs were classified as benign in 21 (78%) patients with mild and 8 (67%) with moderate aortic regurgitation. Diastolic murmurs were rare, occurring in two (14%) with moderate, two (4%) with mild, and three (2%) with no aortic regurgitation (p=0.15). CONCLUSIONS: An isolated systolic murmur is a common auscultatory finding by a noncardiologist in patients with moderate or milder aortic regurgitation. A systolic murmur in patients at risk for aortic valve disease should prompt a more thorough physical examination for aortic regurgitation.

A comparison of treadmill scores to diagnose coronary artery disease.

BACKGROUND: Recently, several treadmill scores have been proposed as means for improving the diagnostic accuracy of the exercise treadmill test (ETT). Questions remain regarding the diagnostic accuracy of treadmill scores when applied to a different patient population than that from which they were derived; furthermore, many treadmill scores have not been compared with one another in the same population. HYPOTHESIS: The diagnostic accuracy of treadmill scores may not be the same. METHODS: A retrospective analysis of data collected prospectively was performed on consecutive patients referred for evaluation of chest pain. All patients underwent a standard ETT followed by coronary angiography. Using angiographic evidence of coronary artery disease (CAD) as a reference, the area under the curve (AUC) of receiver operator characteristic (ROC) plots of the ST response alone, the Duke Treadmill Score (DTS), the Morise score, the Detrano score, the VA score, and a Consensus score consisting of the Morise, Detrano, and VA scores together were calculated and compared. The predictive accuracies of the DTS and the Consensus score to stratify patients for the likelihood of CAD were calculated and compared. RESULTS: In all, 1,282 patients without a prior myocardial infarction had an ETT and coronary angiography. The AUC (+/- standard error) was 0.67+/-0.01 for the ST response, 0.73+/-0.01 for DTS, 0.76+/-0.01 for Detrano score, 0.77+/-0.01 for Morise score, 0.78+/-0.01 for VA score, and 0.78+/-0.01 for Consensus score. The AUC for each treadmill score was significantly higher (z-score > 1.96) than for the ST response alone. The AUC of DTS was significantly lower than all other treadmill scores (z-score > 1.96). The predictive accuracy (+/-95% confidence interval) of the DTS to risk stratify patients into high and low likelihood for CAD was 71 (65-77)%, versus 80 (74-86)% for the Consensus score (p < 0.0001). CONCLUSION: In this population, the DTS remains useful for diagnosing CAD and stratifying for the likelihood of CAD, although it is less accurate than other treadmill scores.

Repair of Superior Vena Caval Perforation during Pacemaker Placement with Video-Assisted Limited Thoracotomy.

Abstract We report a case of a patient who sustained superior vena cava perforation just proximal to the innominate-caval confluence during pacemaker implantation. Because this complication was recognized early and the dilator was left in place, the patient remained hemodynamically stable and successfully underwent a videoscopically assisted repair of the superior vena caval perforation through a limited thoracotomy incision.

Myopericarditis following smallpox vaccination among vaccinia-naive US military personnel.

CONTEXT: In the United States, the annual incidence of myocarditis is estimated at 1 to 10 per 100,000 population. As many as 1% to 5% of patients with acute viral infections involve the myocardium. Although many viruses have been reported to cause myopericarditis, it has been a rare or unrecognized event after vaccination with the currently used strain of vaccinia virus (New York City Board of Health). OBJECTIVE: To describe a series of probable cases of myopericarditis following smallpox vaccination among US military service members reported since the reintroduction of vaccinia vaccine. DESIGN, SETTING, PARTICIPANTS: Surveillance case definitions are presented. The cases were identified either through sentinel reporting to US military headquarters surveillance using the Defense Medical Surveillance System or reports to the Vaccine Adverse Event Reporting System using International Classification of Diseases, Ninth Revision. The cases occurred among individuals vaccinated from mid-December 2002 to March 14, 2003. MAIN OUTCOME MEASURE: Elevated serum levels of creatine kinase (MB isoenzyme), troponin I, and troponin T, usually in the presence of ST-segment elevation on electrocardiogram and wall motion abnormalities on echocardiogram. RESULTS: Among 230,734 primary vaccinees, 18 cases of probable myopericarditis after smallpox vaccination were reported (an incidence of 7.8 per 100,000 over 30 days). No cases of myopericarditis following smallpox vaccination were reported among 95,622 vaccinees who were previously vaccinated. All cases were white men aged 21 years to 33 years (mean age, 26.5 years), who presented with acute myopericarditis 7 to 19 days following vaccination. A causal relationship is supported by the close temporal clustering (7-19 days; mean, 10.5 days following vaccination), wide geographic and temporal distribution, occurrence in only primary vaccinees, and lack of evidence for alternative etiologies or other diseases associated with myopericarditis. Additional supporting evidence is the observation that the observed rate of myopericarditis among primary vaccinees is 3.6-fold (95% confidence interval, 3.33-4.11) higher than the expected rate among personnel who were not vaccinated. The background incidence of myopericarditis did not show statistical significance when stratified by age (20-34 years: 2.18 expected cases per 100,000; 95% confidence interval [CI], 1.90-2.34), race (whites: 1.82 per 100,000; 95% CI, 1.50-2.01), and sex (males: 2.28 per 100,000; 95% CI, 2.04-2.54). CONCLUSION: Among US military personnel vaccinated against smallpox, myopericarditis occurred at a rate of 1 per 12 819 primary vaccinees. Myopericarditis should be considered an expected adverse event associated with smallpox vaccination. Clinicians should consider myopericarditis in the differential diagnosis of patients presenting with chest pain 4 to 30 days following smallpox vaccination and be aware of the implications as well as the need to report this potential adverse advent.