Maria Anna Secknus

Evolution of Dobutamine Echocardiography Protocols and Indications: Safety and Side Effects in 3,011 Studies Over 5 Years

OBJECTIVES This study sought to document the safety of dobutamine stress echocardiography as it has evolved at a single center and to define predictors of adverse events. BACKGROUND The indications and protocol for dobutamine stress testing have evolved over 5 years of clinical use, but the influence of these changes on the safety and side effects of the test is undefined. METHODS Over 5 years, 3,011 consecutive dobutamine stress studies were performed in 2,871 patients, using an incremental protocol from 5 to 40 micrograms/kg body weight per min in 3-min stages, followed by atropine or an additional stage with 50 micrograms/kg per min, if required. Clinical data were gathered prospectively, and hemodynamic and echocardiographic findings were recorded at each stage, including recovery. Dobutamine echocardiography was defined as positive for ischemia in the presence of new or worsening wall motion abnormalities; in the absence of ischemia, failure to attain 85% of age-predicted maximal heart rate was identified as a nondiagnostic result. RESULTS Studies were performed for risk assessment (70%) and symptom evaluation (30%); over the study period, there was an increment in the use of dobutamine echocardiography for preoperative evaluation. Most tests (n = 2,194 [73%]) were terminated due to attainment of peak dose with achievement of target heart rate (> 85% maximal age-predicted heart rate); 455 patients (15%) failed to achieve > 85% maximal predicted heart rate despite maximal doses of dobutamine and atropine. The protocol was stopped prematurely in 230 patients (7.6%) because of side effects, including ventricular (n = 27 [0.9%]) and supraventricular rhythm disorders (n = 22 [0.7%]), severe hypertension (n = 24 [0.8%]) and hypotension or left ventricular outflow tract obstruction (n = 112 [3.8%]). Noncardiac symptoms, such as headache, nausea or anxiety, caused early test termination in 45 patients (1.6%). The remaining tests were stopped because of severe chest pain (n = 106 [3.5%]) or severe ischemia by echocardiography (n = 26 [0.9%]). Serious complications occurred in nine patients, including sustained ventricular tachycardia in five, myocardial infarction in one and other conditions in three requiring hospital admission (sustained supraventricular tachycardia, hypotension, suspected myocardial infarction), but neither ventricular fibrillation nor death occurred. Independent predictors of serious complications could not be defined. Over 5 years, higher dose protocols and more frequent use of atropine have raised the number of diagnostic protocols from 59% to 80%, without increasing the incidence of major side effects. CONCLUSIONS Despite the use of more aggressive protocols and alterations of the indications for testing to include sicker patients, major side effects are a rare complication of dobutamine echocardiography.

Functional status and quality of life in patients with heart failure undergoing coronary bypass surgery after assessment of myocardial viability

OBJECTIVES The aim of this study was to evaluate whether preoperative clinical and test data could be used to predict the effects of myocardial revascularization on functional status and quality of life in patients with heart failure and ischemic LV dysfunction. BACKGROUND Revascularization of viable myocardial segments has been shown to improve regional and global LV function. The effects of revascularization on exercise capacity and quality of life (QOL) are not well defined. METHODS Sixty three patients (51 men, age 66+/-9 years) with moderate or worse LV dysfunction (LVEF 0.28+/-0.07) and symptomatic heart failure were studied before and after coronary artery bypass surgery. All patients underwent preoperative positron emission tomography (PET) using FDG and Rb-82 before and after dipyridamole stress; the extent of viable myocardium by PET was defined by the number of segments with metabolism-perfusion mismatch or ischemia. Dobutamine echocardiography (DbE) was performed in 47 patients; viability was defined by augmentation at low dose or the development of new or worsening wall motion abnormalities. Functional class, exercise testing and a QOL score (Nottingham Health Profile) were obtained at baseline and follow-up. RESULTS Patients had wall motion abnormalities in 83+/-18% of LV segments. A mismatch pattern was identified in 12+/-15% of LV segments, and PET evidence of viability was detected in 30+/-21% of the LV. Viability was reported in 43+/-18% of the LV by DbE. The difference between pre- and postoperative exercise capacity ranged from a reduction of 2.8 to an augmentation of 5.2 METS. The degree of improvement of exercise capacity correlated with the extent of viability by PET (r = 0.54, p = 0.0001) but not the extent of viable myocardium by DbE (r = 0.02, p = 0.92). The area under the ROC curve for PET (0.76) exceeded that for DbE (0.66). In a multiple linear regression, the extent of viability by PET and nitrate use were the only independent predictors of improvement of exercise capacity (model r = 0.63, p = 0.0001). Change in Functional Class correlated weakly with the change in exercise capacity (r = 0.25), extent of viable myocardium by PET (r = 0.23) and extent of viability by DbE (r = 0.31). Four components of the quality of life score (energy, pain, emotion and mobility status) significantly improved over follow-up, but no correlations could be identified between quality of life scores and the results of preoperative testing or changes in exercise capacity. CONCLUSIONS In patients with LV dysfunction, improvement of exercise capacity correlates with the extent of viable myocardium. Quality of life improves in most patients undergoing revascularization. However, its measurement by this index does not correlate with changes in other parameters nor is it readily predictable.

Influence of gender on physiologic response and accuracy of dobutamine echocardiography

Dobutamine echocardiography (DE) has been shown to be safe, feasible, and accurate for identification of coronary artery disease (CAD) in mixed populations. The purpose of this study was to examine gender differences in physiologic response and accuracy of DE. We studied 2,886 consecutive DEs, performed in 2,748 patients, 1,209 of whom (44%) were women. A standard incremental protocol (5 to 40 microg/kg/min in 3-minute stages) was followed by atropine and/or an additional stage with 50 microg/kg/min, if the heart rate response was inadequate. Hemodynamic and echocardiographic findings were recorded at each stage. Three hundred sixty-nine patients without previous cardiac intervention (including 135 women) also underwent cardiac catheterization within 1 year of DE. Significant coronary stenoses (defined angiographically as >50% diameter) were present in 67% of women and 65% of men, of whom 55% and 65%, respectively, had multivessel disease. Women had a higher baseline heart rate (76 +/- 13 vs 73 +/- 14 beats/min, p <0.0001), and showed a more rapid increase in heart rate at low dose, with a higher age-predicted maximum heart rate at peak. This led to test termination at target heart rate but a submaximum dose in 22% of women versus 15% of men (p <0.0001) and less frequent administration of atropine (29% vs 34%, p <0.01). Dose-limiting side effects (8% vs 7%) and submaximum heart rate responses (14% vs 17%) were comparable in men and women. Even after the exclusion of negative DE at submaximal heart rate responses, the overall sensitivity was significantly lower in women than men (78% vs 88%, p <0.05), both for single (72% vs 78%, p <0.05) and for multivessel disease (82% vs 93%, p <0.05). The low specificity in both genders (55% vs 46%) probably reflected post-test referral bias. Thus, physiologic responses to dobutamine stress are comparable in men and women, except for a more rapid heart rate response in women, but the accuracy of DE for diagnosis of CAD in women is less than in men.

Cardiac Outcomes in Coronary Patients With Submaximum Dobutamine Stress Echocardiography

This study evaluated the prediction of cardiac events (cardiac death, myocardial infarction, unstable angina, or late myocardial revascularization) in patients with submaximum responses to dobutamine stress, defined by attainment of <85% age-predicted heart rate. Of 1,772 patients undergoing dobutamine echocardiography over a 2-year period, 425 had a submaximum heart rate response. After exclusion of patients treated with beta-adrenoceptor blocking agents, 255 patients formed the study group. In these patients, the test was terminated after administration of the maximum dose of 40 microg/kg/min of dobutamine with atropine (end of protocol, n = 186), severe angina, ischemic ST-segment changes, or intolerable side effects (n = 69). Dobutamine-induced changes (ischemia, viability, or both) were detected in 46 patients, involving ischemia in 133 segments, viability in 23, and ischemia and viability in 16 segments. Patients were followed for an interval of 28 +/- 17 months; 5 (1.2%) were lost to follow-up. Of the medically treated patients, cardiac events occurred in 73 of 228 (31%), including cardiac death in 25 (11%), nonfatal myocardial infarction in 11 (4.8%), severe unstable angina in 35 (15%), and late revascularization in 2 (0.9%). Cardiac events occurred in 11 of 30 (36%) with inducible abnormalities, and 62 of 198 without inducible abnormalities (31%, p = NS). Thus, cardiac event rates are high in patients with inadequate chronotropic responses to dobutamine stress, irrespective of whether stress-induced changes are detected. A negative dobutamine echocardiogram at submaximum heart rate should be considered nondiagnostic.

Prognosis of patients with vascular disease after clinical evaluation and dobutamine stress echocardiography.

BACKGROUND Coronary disease is an important cause of long-term morbidity in patients needing major vascular surgery. We sought to assess the efficacy of preoperative clinical evaluation and the detection of inducible ischemia for prediction of immediate and long-term cardiac outcomes of patients undergoing vascular surgery. METHODS In 233 patients undergoing vascular procedures, we assessed risk clinically on the basis of Eagles criteria. Dobutamine echocardiography was performed with a standard protocol and results were classified as showing ischemia, scar, or a normal response. Patients were observed perioperatively, and late follow-up (28 +/- 13 months) was completed in all surgical survivors. A composite end point of cardiac death, myocardial infarction, and unstable and progressive angina requiring late revascularization was used to judge event-free survival. RESULTS Of 233 patients undergoing preoperative dobutamine echocardiography, 39 (17%) had inducible ischemia and 36 (15%) had scar. Perioperative events occurred in 8 patients (3%). None of the patients with ischemia had perioperative events, reflecting the effect of revascularization in 9 patients. Late events occurred in 36 patients; ischemia on preoperative stress testing was a predictor of these events even after adjusting for clinical variables and left ventricular dysfunction (relative risk = 3.3; 95% confidence interval 1.6 to 6.8; P =.001). The association of ischemia with clinical predictors was associated with incrementally worse outcome. CONCLUSION In addition to perioperative assessment, the combined use of clinical and dobutamine echocardiographic evaluation may stratify the risk of late cardiac events.

Diagnostic and Prognostic Implications of Left Ventricular Cavity Obliteration Response to Dobutamine Echocardiography

Left ventricular (LV) cavity obliteration during dobutamine echocardiography (DE) indicates a vigorous inotropic response to stress. Such a response may suggest the absence of coronary artery disease (CAD), but a small LV cavity may also preclude recognition of wall motion abnormalities. We sought to determine the frequency, correlates, accuracy, and prognostic value of the LV cavity obliteration response in 336 consecutive patients who underwent coronary angiography within 1 year of DE. Cavity obliteration was defined by contact of the opposite walls in the apical views during DE, and ischemia by detection of a new or worsening wall motion abnormality. Sensitivity was based on comparison with coronary anatomy in 220 patients without prior revascularization. The prognostic implications of cavity obliteration were examined by follow-up of 324 patients (96%) over 23 +/- 9 months for death, myocardial infarction, and late revascularization. Cavity obliteration was present in 86 of the 336 DE studies (26%). Baseline and stress hemodynamics were not predictive of cavity obliteration, which was associated with LV hypertrophy and female gender (p <0.0001), and inversely related to LV systolic dysfunction and use of angiotensin-converting enzyme inhibitors or diuretics (p <0.02). The sensitivity of DE was less in patients with cavity obliteration than the remainder, especially in single vessel (46% vs 92%, p <0.001) but also in multivessel CAD (73% vs 95%, p = 0.01). Irrespective of DE and angiographic results, cavity obliteration was a negative predictor for cardiac events (RR 0.42, 95% confidence interval [CI] 0.21 to 0.87, p = 0.02) and death (RR 0.14, 95% CI 0.02 to 1.09, p = 0.06). Even after exclusion of patients with LV dysfunction, cavity obliteration was an independent predictor of freedom from events (RR 0.41, 95% CI 0.19 to 0.88, p = 0.02). Thus, LV cavity obliteration is a frequent response to DE, which compromises the sensitivity of DE but is correlated paradoxically with a favorable clinical outcome.

Correlation of Preoperative Myocardial Function, Perfusion, and Metabolism With Postoperative Function at Rest and Stress After Bypass Surgery in Severe Left Ventricular Dysfunction

Previous studies of dobutamine echocardiography (DE) and positron emission tomography (PET) showed similar accuracy for predicting improvement in resting wall motion after revascularization, although limited direct comparative data are available. We sought to compare the relative accuracy of detecting contractile reserve, ischemia, perfusion, and myocardial metabolism for predicting functional recovery after coronary bypass surgery in 94 consecutive patients (aged 63+/-11 years) with chronic coronary disease and depressed left ventricular function (ejection fraction 28+/-5%). PET imaging comprised rest and dipyridamole stress myocardial perfusion images, with fluorodeoxyglucose to define metabolism-perfusion mismatch. A standard dobutamine-atropine stress was used, with evaluation of low- and peak-dose echocardiographic responses. Regional function was assessed after 13+/-16 weeks at rest in 68 patients who underwent isolated coronary bypass operation without evidence of perioperative infarction, and at rest and stress in a subgroup of 29 patients. Concordance between methods for evaluating abnormal segments (ischemic, viable, and scar) and accuracy of both tests for predicting improvement in regional function were identified. Concordance between PET and DE for identifying viable or nonviable myocardium was 63% using a 16-segment model. For predicting improved resting function after surgery, the sensitivity of PET (84%) was superior to DE (69%, p<0.001), but DE was more specific (78% vs. 37%, p<0.0001) and more accurate (75% vs. 53%, p<0.001) in predicting recovery at rest. Analysis of postoperative recovery of segmental function during stress also showed the specificity of DE to exceed that of PET (89% vs. 32%, p<0.001). The accuracy of DE was enhanced by evaluation of function during stress (86%, p<0.001), but this was not altered with PET (52%, p = NS). Thus, PET is more sensitive than DE in predicting functional recovery, but DE is more specific than PET. Evaluation of left ventricular functional recovery during stress may be preferable to assessment at rest.