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.     

Myopericarditis: Etiology, management, and prognosis

Acute pericarditis is often accompanied by some degree of myocarditis. In clinical practice both pericarditis and myocarditis coexist because they share common etiologic agents, mainly cardiotropic viruses. The term "myopericarditis" indicates a primarily "pericarditic syndrome" and it is responsible for the majority of cases. The clinical presentation is varied, reflecting the variability of myocardial involvement, that may be focal or diffuse, affecting any or all cardiac chambers. Probably many cases may be subclinical and subtle cardiac symptoms and signs may be overshadowed by the systemic manifestations of the viral infection. Echocardiography is essential for the diagnosis of left ventricular dysfunction in even subclinical cases and for follow-up of patients with apparently normal left ventricular function. Magnetic resonance imaging holds promise for an effective non-invasive diagnostic tool. Either for acute pericarditis or myopericarditis there is a lack for adequate controlled clinical trials. In myopericarditis the use of NSAID should be cautious, because in animal models of myocarditis, NSAID are not effective and may actually enhance the myocarditic process and increase mortality. In clinical practice lower anti-inflammatory doses are mainly considered to control symptoms. The natural history of myopericarditis in large populations is not known with accuracy. On follow-up, the majority of these cases had objective normalization of echocardiography, electrocardiography, laboratory testing, and functional status, although up to 14% may report atypical, non-limiting chest discomfort. Unfortunately, few data have been published on myopericarditis, the paper reviews current available evidence on the presentation, management, and prognosis of myopericarditis.     

Acute myopericarditis after diphtheria, tetanus, and polio vaccination

We report the first case of myopericarditis after triple vaccination against diphtheria, tetanus, and poliovirus in a young adult. He presented with fever, acute chest pain, and diffuse ST-segment elevation 2 days after vaccination. Two-dimensional echocardiography findings were normal. Endomyocardial biopsy showed interstitial edema with diapedesis of erythrocytes. Laboratory findings showed inflammatory syndrome and elevated circulating immune complexes. He recovered within a few days with high-dose aspirin treatment and was without complications at 3-month follow-up. We discuss the different hypotheses for infective or hypersensitivity myocarditis.     

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.     

Cost-effectiveness of diagnostic strategies for patients with chest pain.

BACKGROUND: Many noninvasive tests exist to determine whether patients should undergo coronary angiography. The routine use of coronary angiography without previous noninvasive testing is typically not advocated. OBJECTIVE: To determine the cost-effectiveness of diagnostic strategies for patients with chest pain. DESIGN: Cost-effectiveness analysis. DATA SOURCES: Published data. TARGET POPULATION: Patients who present with chest pain, have no history of myocardial infarction, and are able to perform an exercise stress test. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: No testing, exercise electrocardiography, exercise echocardiography, exercise single-photon emission computed tomography (SPECT), and coronary angiography alone. OUTCOME MEASURES: Quality-adjusted life expectancy, lifetime cost, and incremental cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: The incremental cost-effectiveness ratio of routine coronary angiography compared with exercise echocardiography was $36,400 per quality-adjusted life-year (QALY) saved for 55-year-old men with typical angina. For 55-year-old men with atypical angina, exercise echocardiography compared with exercise electrocardiography cost $41,900 per QALY saved. If adequate exercise echocardiography was not available, exercise SPECT cost $54,800 per QALY saved compared with exercise electrocardiography for these patients. For 55-year-old men with nonspecific chest pain, the incremental cost-effectiveness ratio of exercise electrocardiography compared with no testing was $57,700 per QALY saved. RESULTS OF SENSITIVITY ANALYSIS: On the basis of a probabilistic sensitivity analysis, there is a 75% chance that exercise echocardiography costs less than $50,900 per QALY saved for 55-year-old men with atypical angina. CONCLUSIONS: Exercise electrocardiography or exercise echocardiography resulted in reasonable cost-effectiveness ratios for patients at mild to moderate risk for coronary artery disease in terms of age, sex, and type of chest pain. Coronary angiography without previous noninvasive testing resulted in reasonable cost-effectiveness ratios for patients with a high pretest probability of coronary artery disease.     

Eosinophilic-lymphocytic myocarditis after smallpox vaccination

Smallpox is an eradicated viral disease that has re-emerged as a potential bioterrorism threat. Smallpox vaccination was historically the most effective defence measure against wild smallpox virus. The risk of myopericarditis after vaccination might limit this option. We report a case of biopsy-proven eosinophilic-lymphocytic myocarditis diagnosed in vivo with histological evidence for eosinophil-mediated cardiac myocyte necrosis shortly after smallpox vaccination. Furthermore, we report a beneficial haemodynamic response to high-dose corticosteroids. A better understanding of the aberrant immune mechanism of myocyte injury after smallpox vaccination might improve the risk/benefit assessment for people considering smallpox vaccination and better smallpox vaccines in the future.     

The incremental prognostic value of pharmacological stress echo over exercise electrocardiography in women with chest pain of unknown origin.

AIMS: The value of exercise electrocardiography in evaluating women with suspected coronary artery disease is limited. Conversely, stress echocardiography is effective for both diagnostic and prognostic purposes in females. The purpose of the study was to determine the relative prognostic value of exercise electrocardiography and pharmacological stress echocardiography in a cohort of women with chest pain of unknown origin, in order to verify whether criteria could be established for the daily non-invasive evaluation of such a low-risk profile population. METHODS AND RESULTS: Exercise electrocardiography and pharmacological stress echocardiography (171 dipyridamole, 73 dobutamine) were performed in 244 women (age 60+/-10 years) with chest pain and known coronary artery disease. A positive result of exercise electrocardiography (ST-segment shift > or =1 mm at 80 ms after the J point) was detected in 95 patients; a positive result of stress echocardiography (new regional wall motion abnormalities) was observed in 33 patients. During follow-up (36+/-18 months), two deaths, five infarctions, seven unstable anginas, and 11 coronary revascularizations occurred. Using Cox analysis, the positive result of stress echocardiography (odds ratio=40.1) alone, was independently related to hard cardiac events (death, infarction). With spontaneous cardiac events (death, infarction, and unstable angina) as end-points, the multivariate prognostic predictors were a positive result of stress echocardiography (odds ratio=37.0), a family history of coronary artery disease (odds ratio=4.1), typical chest pain (odds ratio=3.7), and a positive exercise electrocardiography result with a rate-pressure product < or =20 000 (odds ratio=3.5). By adopting an interactive stepwise procedure, the prognostic value of stress echocardiography was incremental to that of clinical and exercise electrocardiography data. Nevertheless, the negative result of exercise electrocardiography and pharmacological stress predicted a very high and comparable (P=ns) 24-month survival rate when both hard and spontaneous cardiac events were taken as end-points. CONCLUSIONS: In women with chest pain, stress echocardiography is a strong and independent prognostic indicator, incremental to that shown by exercise electrocardiography. However, the two tests have a similar high negative predictive value in this population. Therefore, exercise electrocardiography has to be considered the initial approach and the only test when the result is negative, whereas stress echocardiography is warranted in selected conditions, including those in women with uninterpretable electrocardiograms, those unable to exercise maximally, and those with an ambiguous or ischaemic response to exercise electrocardiography.     

Stress echo in chest pain unit: the SPEED trial

BACKGROUND: Emergency room (ER) evaluation of patients with acute chest pain and non-diagnostic electrocardiography (ECG) remains a frequent and difficult problem. AIM: To assess safety and prognostic implications of pharmacological stress echocardiography in the ER chest pain unit (CPU). METHODS: A total of 552 patients (321 males, age 58+/-12.6 years) with acute chest pain, negative serial enzymes and/or troponin, and ECG recordings, and normal/unchanged resting left ventricular function were prospectively enrolled and underwent pharmacological (dipyridamole or dobutamine) stress echo. Six echo labs that had passed the preliminary quality control for stress echo reading entered the study. Follow-up was obtained in all patients after a median period of 13 months. RESULTS: No significant adverse events were observed during the test. Stress echocardiography was negative in 502 patients (91%) and positive in 50 (9%). The 502 patients with negative stress echocardiography were discharged with no or unchanged anti-ischemic medications. While the 50 patients with positive stress echo were admitted to the coronary care unit, 44 of these underwent coronary angiography with the result that 42 out of 44 showed significant coronary artery disease. There were 45 events in the follow-up: six in the 502 patients with negative and 39 in the 50 patients with positive stress echo (1.2% vs. 78%, p<0.001). The negative predictive value of stress echocardiography was 98.8% for all events and 99.6% for hard events. CONCLUSIONS: Stress echocardiography is a feasible, safe, and effective tool for early stratification of patients admitted to the ER with acute chest pain and non-ischemic ECG and resting echo.     

Clinical,exercise electrocardiographic,and pharmacologic stress echocardiographic findings for risk stratification of hypertensive patients with chest pain

Exercise electrocardiography (ECG) is of limited usefulness in hypertensive patients, whereas pharmacologic stress echocardiography can provide diagnostic and prognostic information. The aim of this study was to compare the prognostic value of clinical data, exercise ECG, and pharmacologic stress echocardiography in hypertensive patients with chest pain and to identify the best strategy for their risk stratification. Three hundred sixty-seven hypertensive patients (189 men, age 61 +/- 9 years) with chest pain of unknown origin underwent exercise ECG and pharmacologic stress echocardiography (237 with dipyridamole and 130 with dobutamine) and were followed up for 31 +/- 24 months. Positive exercise ECG (ST-segment shift of > or =1 mm at 80 ms after the J point) and stress echocardiography (new wall motion abnormalities) were found in 130 (35%) and 86 (23%) patients, respectively. During follow-up, there were 13 deaths and 16 myocardial infarctions. Additionally, 43 patients underwent coronary revascularization and were censored accordingly. Of 12 clinical, electrocardiographic, and echocardiographic variables analyzed, a positive result of stress echocardiography was the only multivariate predictor of either death (hazard ratio [HR] 4.7, 95% confidence interval [CI] 1.5 to 14.5, p = 0.007) or hard events (death, myocardial infarction) (HR 4.1, 95% CI 1.8 to 9.3, p = 0.0009). Using an interactive stepwise procedure, stress echocardiography provided additional prognostic information to clinical evaluation and exercise ECG. However, the negative predictive value of the 2 tests was similarly (p = NS) high in assessing 4-year event-free survival. In conclusion, a negative exercise electrocardiographic test identifies low-risk hypertensive patients with chest pain and should be the first-line approach for risk stratification. In contrast, positive exercise ECG is unable to distinguish between patients with different levels of risk. In this case, stress echocardiography provides strong and incremental prognostic power over clinical and exercise electrocardiographic data.     

Usefulness of technetium-99m tetrofosmin single-photon emission computed tomography for short-term risk stratification in patients with acute chest pain in the emergency room

OBJECTIVES: High-risk patients with acute coronary syndrome are difficult to distinguish from low-risk patients with chest pain in the emergency room. Technetium-99m (99mTc) tetrofosmin single-photon emission computed tomography (SPECT) was investigated to exclude high-risk patients with chest pain in the emergency room. METHODS: 99mTc-tetrofosmin SPECT was evaluated using a four-point scoring system in 228 patients (144 men, 84 women, mean age 68 +/- 12 years) with chest pain. Negative was defined as the myocardial segments with a defect score (DS) of < 2. The patients were divided into two groups; the negative group with DS < 2 (n = 78) and the positive group with DS > or = 2 (n = 150). Cardiac events (cardiac death, acute myocardial infarction and refractory angina) were evaluated within 30 days of onset. ST-segment elevation or depression > or = 0.1 mV was defined as positive in electrocardiography. The results of SPECT were compared with those of electrocardiography, transthoracic echocardiography and serum cardiac markers (troponin T and creatine kinase-MB) in 95 patients. RESULTS: The negative group had very few cardiac events (three patients with refractory angina) (3.8%). The negative predictive value of cardiac events evaluated by electrocardiography was calculated as 83.1%, whereas the negative predictive value by SPECT was 96.2% (p < 0.01). In addition, the negative predictive value of acute myocardial infarction by SPECT was 100%. The negative predictive values of cardiac events evaluated by SPECT, electrocardiography, transthoracic echocardiography and serum cardiac markers were 95.8%, 81.5% (vs 99mTc-tetrofosmin; NS), 84.9% (NS) and 60.4% (p < 0.05), respectively. CONCLUSIONS: 99mTc-tetrofosmin SPECT is a useful method to exclude high-risk patients among patients with chest pain in the emergency room.     

Evaluation of mild acute infectious myocarditis

The diagnosis of acute mild myocarditis in vaguely defined. Therefore we studied 185 consecutive young men in military service with electrocardiographic changes arousing a suspicion of myocarditis in connection with an acute infectious disease. It was possible to classify 160 patients into seven electrocardiographic groups; definite or probable myocarditis was observed in 104 patients. The electrocardiographic patterns considered characteristic for acute myocarditis were: ST segment elevations followed by T wave inversions; gradually changing T wave inversions not corrected by beta blockade; and ventricular extrasystoles more than 10 per minute triggered by acute infection. Thirty-nine subjects without myocarditis had "functional" T wave abnormalities completely normalised by beta blockade, or stable T wave inversion. The leading symptoms in acute myocarditis were fatigue and chest pains; loud S3 gallop, paradoxical cardiac pulsation, pericardial friction rub, or enlargement of the heart were noted altogether in 50% of the patients. Echocardiography disclosed segmental wall motion abnormalities related to the T wave inversions. Serum creatine kinase MB fraction increased in 70% of the acute myopericarditis patients during the ST segment elevation stage. In the non-myocarditis groups the clinical and pertinent laboratory findings remained normal. Thus, we noted in clinically mild acute infectious myocarditis clear-cut and early signs of myocardial dysfunction, suggesting that the direct and often local viral invasion of the myocardium is the basic pathogenetic mechanism. The present electrocardiographic classification based on serial tracings and beta blockade proved useful in the evaluation of patients suspected of having mild acute myocarditis.     

Evaluation of mild acute infectious myocarditis.

The diagnosis of acute mild myocarditis in vaguely defined. Therefore we studied 185 consecutive young men in military service with electrocardiographic changes arousing a suspicion of myocarditis in connection with an acute infectious disease. It was possible to classify 160 patients into seven electrocardiographic groups; definite or probable myocarditis was observed in 104 patients. The electrocardiographic patterns considered characteristic for acute myocarditis were: ST segment elevations followed by T wave inversions; gradually changing T wave inversions not corrected by beta blockade; and ventricular extrasystoles more than 10 per minute triggered by acute infection. Thirty-nine subjects without myocarditis had "functional" T wave abnormalities completely normalised by beta blockade, or stable T wave inversion. The leading symptoms in acute myocarditis were fatigue and chest pains; loud S3 gallop, paradoxical cardiac pulsation, pericardial friction rub, or enlargement of the heart were noted altogether in 50% of the patients. Echocardiography disclosed segmental wall motion abnormalities related to the T wave inversions. Serum creatine kinase MB fraction increased in 70% of the acute myopericarditis patients during the ST segment elevation stage. In the non-myocarditis groups the clinical and pertinent laboratory findings remained normal. Thus, we noted in clinically mild acute infectious myocarditis clear-cut and early signs of myocardial dysfunction, suggesting that the direct and often local viral invasion of the myocardium is the basic pathogenetic mechanism. The present electrocardiographic classification based on serial tracings and beta blockade proved useful in the evaluation of patients suspected of having mild acute myocarditis.     

Clinical outcome and left ventricular function 23 years after acute coxsackie virus myopericarditis

The clinical outcome of 18 patients, who presented with a Coxsackie virus myopericarditis in 1965, was evaluated 23 years later. Five patients had died, two of them had had heart failure. Thirteen patients and 23 healthy control subjects underwent exercise testing with gas exchange analysis. Left ventricular (LV) peak filling rate (PFR) was estimated by digitized M-mode echocardiography. Left ventricular ejection fraction was measured at rest and during exercise by radionuclide angiography. All patients were free of cardiac symptoms. Their clinical examination and the chest X-ray were normal. Peak oxygen consumption was not decreased in the patient group compared with the control group. PFR was significantly lower in the patient group than in the control group, 10.2 +/- 0.4 vs 13.2 +/- 0.4 cm s-1, P less than 0.001 (mean +/- SEM). LV ejection fraction was normal at rest in all patients (58 +/- 1%). An abnormal LV ejection fraction response to exercise was observed in two patients. Our data indicate that long-term prognosis after acute Coxsackie virus myopericarditis is good in a majority of patients.     

Prognostic significance of left ventricular aneurysms with normal global function caused by myocarditis

OBJECTIVES: To evaluate the prognosis of left ventricular (LV) aneurysms with normal global function caused by myocarditis. BACKGROUND: LV aneurysms may result from idiopathic or viral myocarditis. The prognosis of inflammatory LV aneurysms when associated with a normal cardiac function is unknown. METHODS: Among 353 patients with a histologic diagnosis of myocarditis, 12 (3.3%) had single or multiple localized LV aneurysms (length, 10.6 +/- 3.1 mm; width, 7.4 +/- 4.2 mm) with normal cardiac function. Presenting symptoms were ventricular tachycardia (VT) in nine patients and unexplained chest pain in three. All patients underwent laboratory tests and noninvasive and invasive cardiac examinations, including biventricular endomyocardial biopsy. RESULTS: In all patients, LV endomyocardial biopsy specimen showed a lymphocytic myocarditis with focal intense myocytolysis or damage of intramural vessels, whereas right ventricular biopsy was diagnostic for myocarditis only in three. Serologic study suggested a viral infection in 3 patients and an immunologic disorder in 2, although it was negative in 7. Treatment included antiarrhythmics in 9 patients with VT, ss-blockers in 1 with chest pain, and immunosuppression (prednisone and azathioprine for 5 months) in 4 with active myocarditis (2 with chest pain and 2 with VT). At intermediate-term follow-up (mean, 53 months; range, 12 to 120 months), LV function was persistently normal in all patients, with an LV aneurysm occlusion being observed in two patients. All patients were asymptomatic, with no VT recurrence or major clinical events. None required implantable electrical devices or a surgical intervention. CONCLUSIONS: LV aneurysms with normal global function caused by myocarditis are an uncommon benign entity in which major therapeutic regimens are usually unnecessary.     

Stress echocardiography in the evaluation of women presenting with chest pain syndrome: a randomized, prospective comparison with electrocardiographic stress testing

OBJECTIVE: To evaluate the relative value of three stress testing modalities for establishing the presence of coronary artery disease in women presenting with chest pain. BACKGROUND: Echocardiographic testing modalities have the potential to be more effective than standard electrocardiographic stress testing (EST), but they require prospective evaluation. METHODS: Patients with no cardiac history and at least two cardiac risk factors were randomly assigned to one of three initial diagnostic strategies: treadmill EST (n=54), treadmill echocardiographic stress testing (ExE) (n=57) or dobutamine stress echocardiography (DSE) (n=47). Patients were followed prospectively for 28.1+/-14.2 months. The nature of the presenting chest pain was established clinically. RESULTS: Twelve patients (7.6%) were determined to have had cardiac chest pain, 128 patients (81.0%) received a diagnosis of noncardiac chest pain and 18 patients (11.4%) had indeterminate results. The echocardiographic testing modalities were associated with fewer indeterminate results than was EST (two of 104 [1.9%] versus 13 of 54 [24.1%]). All modalities were highly effective in excluding cardiac chest pain, with negative predictive values of 91.3%, 83.7% and 88.4%, respectively, for EST, DSE and ExE. The proportion of cases for which both definitive and accurate results were provided was 92.9% for DSE, 82.4% for ExE and 67.3% for EST. CONCLUSIONS: The results support the favourable prognosis of women presenting with chest pain syndrome and the reliability of negative results obtained with any of the testing modalities. Echocardiographic testing modalities are more likely than EST to provide both definitive and accurate results and would, therefore, seem to be the superior primary noninvasive testing modality in this patient population.     

Dobutamine stress echocardiography in the diagnosis of coronary artery disease in women with chest pain: comparison with different noninvasive tests

BACKGROUND: Diagnosis of coronary artery disease(CAD) in women remains elusive. The classical diagnostic armamentarium has been found to be very limited. Dobutamine stress echocardiography has emerged as a powerful test in assessing CAD in the general population, but most studies failed to include women. HYPOTHESIS: The accuracy of dobutamine stress echocardiography in the diagnosis of CAD in women with chest pain is high and superior to dipyridamole echocardiography, exercise electrocardiography, and sestamibi single-photon emission tomography (MIBI-SPECT) scintigraphy. METHODS: We studied 99 consecutive women with chest pain and no previous history of CAD who underwent dobutamine echocardiography and coronary angiography. We also compared these results with those of dipyridamole echocardiography in 63 patients. exercise stress testing in 83 (48 conclusive), and MIBI-SPECT scintigraphy during dobutamine infusion in 54. RESULTS: Significant CAD was found in 42 women. Sensitivity and specificity of dobutamine stress echocardiography were 69 and 89%, respectively. Dipyridamole echocardiography showed similar accuracy (sensitivity 72% and specificity 94%). Finally, sensitivity of exercise test and MIBI-SPECT was similar (76 and 88%, respectively) and specificity was lower (53 and 57%, respectively). After excluding patients known to have a high incidence of false positive results, MIBI-SPECT specificity rose up to 80%. CONCLUSION: Dobutamine stress echocardiography and dipyridamole echocardiography bear a high diagnostic accuracy in women with chest pain. MIBI-SPECT is also a useful tool after excluding subgroups with a high incidence of false positive results.     

Clinical relevance of chest pain during dobutamine stress echocardiography in women.

BACKGROUND: Dobutamine stress echocardiography (DSE) is commonly used for diagnosis and management of patients with known or suspected coronary artery disease. Chest pain occurring during DSE potentially provides additional diagnostic accuracy. Our experience suggests that chest pain occurs frequently in women undergoing DSE. HYPOTHESIS: It was the purpose of this study to determine the frequency with which chest pain occurs in women undergoing DSE and the relation to inducible ischemia or coronary artery stenosis. METHODS: To determine the prevalence and clinical significance or chest pain during DSE, we reviewed the records of 154 consecutive women undergoing DSE in our laboratory. Of these, 59 patients (37.5%) also underwent coronary angiography. The presence or absence of chest pain was correlated with ECG changes, left ventricular wall motion abnormalities during DSE, and coronary stenosis by angiography. RESULTS: Forty-one women (26%) developed chest pain during DSE. Patients experiencing chest pain were older (58.5 +/- 9.3 vs. 54.9 +/- 12.6; p = 0.05), and had lower resting heart rates (71 +/- 12.2 vs. 77.9 +/- 14.9; p = 0.008), but received similar maximum doses of dobutamine and reached comparable peak heart rates (131.1 +/- 17.4 vs. 133.5 +/- 21.7; p = NS). Patients with chest pain more commonly exhibited ST-segment depression > or = 1 mm during dobutamine infusion (13/41, 32%, vs. 17/113, 15%; p = 0.02), but chest pain showed no statistically significant correlation with abnormal DSE or with coronary stenosis. CONCLUSIONS: In women undergoing DSE, chest pain occurs in 26% and does not appear to be related to inducible myocardial ischemia. Electrocardiographic changes occur more frequently in patients who experience chest pain, but are also often unrelated to inducible myocardial ischemia.     

Pre-event smallpox vaccination for healthcare workers revisited--the need for a carefully screened multidisciplinary cadre.

As healthcare institutions are a focus of smallpox transmission early in an epidemic, several mathematical models support pre-event smallpox vaccination of healthcare workers (HCWs). The deciding factor for HCW voluntary vaccination is the risk of disease exposure versus the risk of vaccine adverse events. In a United States military population, with careful screening to exclude atopic dermatitis/eczema and immunosuppression, over 1 million vaccinia (smallpox) vaccinations were delivered with one fatality attributed to vaccination. Among 37901 United States civilian volunteer HCWs vaccinated, 100 serious adverse events were reported including 10 ischemic cardiac episodes and six myocardial infarctions - two were fatal. This older population had a higher rate of adverse events due to age-related coronary artery disease. T-cell mediated inflammatory processes induced by live vaccinia vaccination may have a role in the observed acute coronary artery events. With exclusion of individuals at risk for coronary artery disease, atopic dermatitis/eczema, and immunosuppression, HCWs can be smallpox vaccinated with minimal risk. A carefully screened multidisciplinary cadre (physician, nurse, infection control practitioner, technician), pre-event vaccinated for smallpox, will supply the necessary leadership to alleviate fear and uncertainty while limiting spread and initial mortality of smallpox.     

Peripartum cardiomyopathy: clinical, echocardiographic and biopsy aspects

In order to characterize the features of peripartum cardiomyopathy, clinical, echocardiographic and right ventricular endomyocardial bioptic data obtained from 6 patients (pts) (age range: 34.1 +/- 5.5. yrs) who fulfilled peripartum cardiomyopathy diagnostic criteria, were analyzed. Five of these pts had clinical and non-invasive studies for a mean period of 41.6 +/- 59.6 months. All but one were multiparous. Five developed heart failure one month before delivery. Three patients had active myocarditis at endomyocardial biopsy and were treated with immunosuppressive therapy. At follow-up, 3 pts improved by two or three grades of the NYHA functional classification. All 3 showed a reduction in the left ventricular end diastolic diameter (from 3.9 +/- 0.4 to 3.4 +/- 0.3 cm/m2) and a normalization of the shortening fraction in 2 (from 15 to 36% and from 13 to 46% respectively) at echocardiography. These two patients had active myocarditis at the first endomyocardial biopsy. At follow-up, all 3 pts with active myocarditis showed histological evidence of healed myocarditis. In conclusion, peripartum cardiomyopathy is characterized by a high incidence of active myocarditis and improvement seems more frequent in this subgroup of pts.     

Safety and prognostic value of early dobutamine-atropine stress echocardiography in patients with spontaneous chest pain and a non-diagnostic electrocardiogram.

AIMS: To risk stratify and shorten hospital stay in patients with spontaneous (resting) chest pain and a non-diagnostic electrocardiogram (ECG). METHODS AND RESULTS: The study comprised 102 patients (mean age 58+/-12 years, 67 men) with spontaneous chest pain and a non-diagnostic ECG. Forty-three patients had suspected coronary artery disease and 59 had known (but of unknown actual significance) coronary artery disease. All patients underwent serial creatine kinase enzyme measurements, continuous ECG monitoring for at least 12 h and early dobutamine-atropine stress echocardiography in patients with negative creatine kinase enzymes and normal findings at ECG monitoring. Dobutamine-atropine stress echocardiography was considered positive in patients with new or worsening wall thickening abnormalities. Patients with negative dobutamine-atropine stress echocardiography were discharged after the test. In-hospital and 6 month follow-up events noted were cardiac death, non-fatal myocardial infarction, unstable angina, and coronary artery bypass surgery or angioplasty. Thirteen patients had evidence of evolving myocardial infarction by elevated creatine kinase enzymes, or unstable angina by ECG monitoring. In the remaining 89 patients, dobutamine-atropine stress echocardiography was performed after a median observation period of 31 h (range 12-68 h). During dobutamine-atropine stress echocardiography no serious complications (death, non-fatal myocardial infarction, sustained ventricular tachycardia or ventricular fibrillation) occurred. Dobutamine-atropine stress echocardiography results were of poor quality in three, non-diagnostic in six, negative in 44 and positive in 36 patients. In the 80 patients with diagnostic dobutamine-atropine stress echocardiography, variables associated with in-hospital events (n=7) were history of exertional angina (P<0. 005), chest pain score (P<0.005), stress-induced angina (P<0.001) and positive dobutamine-atropine stress echocardiography (P<0.005). Variables associated with follow-up events (n=11) were history of exertional angina (P<0.05), chest pain score (P<0.001), stress-induced angina (P<0.01) and positive dobutamine-atropine stress echocardiography (P<0.01). At multivariate analysis the only significant predictor of events was positive dobutamine-atropine stress echocardiography (P<0.01). CONCLUSION: Early dobutamine-atropine stress echocardiography may safely distinguish between low- and high-risk subsets for subsequent cardiac events in patients with spontaneous chest pain and a non-diagnostic ECG.