Dobutamine Stress Echocardiography Ischemia as a Predictor of the Placebo-Controlled Efficacy of Percutaneous Coronary Intervention in Stable Coronary Artery Disease: The Stress Echocardiography-Stratified Analysis of ORBITA.

BACKGROUND: Dobutamine stress echocardiography is widely used to test for ischemia in patients with stable coronary artery disease. In this analysis, we studied the ability of the prerandomization stress echocardiography score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina). METHODS: One hundred eighty-three patients underwent dobutamine stress echocardiography before randomization. The stress echocardiography score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of prerandomization stress echocardiography to predict the placebo-controlled effect of PCI on response variables was tested by using regression modeling. RESULTS: At prerandomization, the stress echocardiography score was 1.56±1.77 in the PCI arm (n=98) and 1.61±1.73 in the placebo arm (n=85). There was a detectable interaction between prerandomization stress echocardiography score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echocardiography score (Pinteraction=0.031). With our sample size, we were unable to detect an interaction between stress echocardiography score and any other patient-reported response variables: freedom from angina (Pinteraction=0.116), physical limitation (Pinteraction=0.461), quality of life (Pinteraction=0.689), EuroQOL 5 quality-of-life score (Pinteraction=0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class (Pinteraction=0.693), and treadmill exercise time (Pinteraction=0.426). CONCLUSIONS: The degree of ischemia assessed by dobutamine stress echocardiography predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echocardiography abnormality caused by a stenosis, the greater the reduction in symptoms from PCI. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02062593.

Beta adrenergic receptor blockade causing severe left ventricular systolic dysfunction during dobutamine stress echocardiography in a patient with no structural heart disease.

A 41-year-old woman with a history of neurocardiogenic syncope treated with beta-blockers was admitted with chest pain. Dobutamine echocardiogram images demonstrated decreased global LV systolic wall motion and thickening. Coronary angiograms were normal. Beta-blockers were stopped and dobutamine stress echocardiogram (DSE) was repeated. Dobutamine images demonstrated increased global LV systolic wall motion and thickening. Beta-blockers were restarted and again dobutamine produced global LV dysfunction. This case suggests that DSE wall motion response may be falsely abnormal in a patient on beta-blockers. Physicians should be aware of this possibility when interpreting dobutamine echocardiography in patients taking beta-blockers.

Dobutamine-induced mechanical alternans is a marker of poor prognosis in idiopathic dilated cardiomyopathy.

1. To date, few prognostic indicators for ambulatory patients with idiopathic dilated cardiomyopathy (IDCM) have been identified. The purpose of the present study was to investigate the relationship between the occurrence of dobutamine-induced mechanical alternans (MA) and prognosis in ambulatory patients with IDCM. 2. Left ventricular pressure was measured during right atrial pacing and after intravenous infusion of dobutamine at incremental doses in 90 ambulatory patients with IDCM in sinus rhythm. Endomyocardial biopsy specimens were also obtained for quantitative analysis of gene expression. The patients were followed up for a mean of 2.5 years. 3. Patients were classified into three groups: (i) 60 patients who exhibited neither pacing- nor dobutamine-induced MA (Group N); (ii) 20 patients who manifested only pacing-induced MA (Group P); and (iii) 10 patients who developed both pacing- and dobutamine-induced MA (Group D). The sarcoplasmic/endoplasmic reticulum calcium ATPase 2a:phospholamban mRNA ratio was significantly higher in Group D patients than in patients in Groups N or P. Multivariate analysis revealed that dobutamine-induced MA (odds ratio 4.05; 95% confidence interval 1.35-12.2) was a significant independent predictor of cardiac events. Cardiac event-free survival in Group D was significantly lower than in Groups N or P, as determined by Kaplan-Meier analysis (P=0.002). 4. The occurrence of dobutamine-induced MA is a potentially useful clinical predictor of poor prognosis in ambulatory patients with IDCM in sinus rhythm.

Pronounced improvement in systolic and diastolic ventricular long axis function after treatment with metoprolol.

BACKGROUND: Although it is well known that left ventricular (LV) function improves after treatment with beta-blockers in heart failure, little attention has been paid to the effects on LV long axis (LAX) function. AIMS: To evaluate LV LAX function after treatment with metoprolol, and to assess whether LV LAX contractile reserve could predict future long-term improvement. METHODS: Twenty-four heart failure patients were randomised to metoprolol or placebo for 6 months, followed by 6 months of open treatment with metoprolol. Rest and dobutamine stress echocardiography (DSE) was performed before and after each treatment period. RESULTS: After treatment with metoprolol, LV LAX function improved significantly, systolic velocity from 29+/-8 to 32+/-15 mm/s, p<0.01 (metoprolol) vs. 28+/-7 to 28+/-11 mm/s, ns (placebo); atrioventricular plane fractional shortening (AVP-FS) from 5.4+/-2.1 to 7.4+/-2.7%, p<0.001 (metoprolol) vs. 5.9+/-2.1 to 5.8+/-2.9%, ns (placebo). The improvement in function was maintained during DSE. LV LAX contractile reserve could not predict treatment response; the treatment effect on LV LAX function was significantly greater than the contractile reserve at baseline. The relative improvement in LV LAX function after metoprolol was 38%, compared with a 20% improvement in LV ejection fraction (EF). CONCLUSION: A significant improvement in LV LAX function was observed after treatment with metoprolol. AVP-FS and systolic velocities increased significantly, and to a greater extent than LVEF.

Right ventricular function during pharmacological and exercise stress testing in horses.

The disproportionate rise of pulmonary artery pressure compared to systemic blood pressure during exercise can lead to detrimental right ventricular remodelling in endurance athletes. Horses may act as an extreme model of these athletic cardiovascular adaptations, as they show a three fold increase in pulmonary pressures during exercise. Right ventricular function was examined in ten healthy horses using post-exercise and pharmacological stress echocardiography in a randomised cross-over design. Exercise testing was performed on a treadmill while pharmacological testing was performed using an atropine-dobutamine infusion. Heart rate, systemic blood pressure and cardiac output during echocardiography were similar post-exercise compared to maximal pharmacological stress. Systolic pulmonary artery pressure was significantly higher during the exercise test (121±15mmHg) and during immediate post-exercise echocardiography (93±10mmHg) compared to maximal pharmacological stress (69±12mmHg). Right ventricular diameters as well as the ratio of systolic right to left ventricular area were higher post-exercise. Right ventricular fractional area change was significantly decreased post-exercise (40.5±6.2%) compared to a significant increase during pharmacological stress echocardiography (72.6±7.3%). Serum cardiac troponin I concentration was significantly higher 2h after the pharmacological test compared to baseline values and post-exercise, although the highest value was found post-exercise in the horse with the highest systolic pulmonary artery pressure and lowest right ventricular fractional area change. Pharmacological stress testing is not recommended in further studies on right ventricular adaptations in athletic horses, as this does not reproduce the effects of exercise.

Strain Imaging with a Bull's-Eye Map for Detecting Significant Coronary Stenosis during Dobutamine Stress Echocardiography.

BACKGROUND: Accurate visual assessment of wall motion during dobutamine stress echocardiography (DSE) requires expertise; strain stress echocardiography thus has potential for the objective and reliable evaluation of stress-induced wall motion abnormalities. The aim of this study was to test the hypothesis that strain imaging also requires expertise. Diagnostic accuracy for significant coronary artery disease was compared between visual and strain analysis with a bull's-eye map, and the effect of expertise on readers' accuracy during DSE was determined. METHODS: Thirty-seven patients who underwent both DSE and coronary angiography within 6 months were retrospectively selected. Three experts and two fellows performed visual and two-dimensional speckle-tracking analysis using vendor-dependent (GE) software in three apical views. A bull's-eye map of longitudinal strain and a postsystolic shortening map were generated at baseline and peak stress. Significant coronary stenosis was defined as a >1% reduction in longitudinal strain with an increase in postsystolic shortening of at least two contiguous segments in the specific coronary artery territory at peak stress compared with baseline. RESULTS: Twenty-five patients had significant coronary artery disease (>70% stenosis on coronary angiography), including 17 with left anterior descending coronary artery stenosis and 19 with non-left anterior descending coronary artery stenosis. Overall, strain imaging provided no additional benefit over visual analysis in detecting significant stenosis per patient and per vessel among experts and fellows. Strain analysis by the fellows had significantly lower specificity and accuracy compared with the experts. CONCLUSIONS: Expertise affects strain evaluation for detecting significant coronary artery disease during DSE.

Análise da Segurança e Exequibilidade do Ecocardiograma sob Estresse com Dobutamina em Dez Mil e Seis Exames de uma População Geral / Analysis of the Safety and Feasibility of Dobutamine Stress Echocardiography in Ten Thousand and Six Tests of a General Population

Fundamento: Durante o ecocardiograma sob estresse com dobutamina, podem ocorrer efeitos adversos e exames inconclusivos. Objetivo: Avaliar em uma grande população geral a segurança e a exequibilidade do ecocardiograma sob estresse com dobutamina. Métodos: Estudo de 10.006 ecocardiogramas sob estresse com dobutamina realizados no período de julho de 1996 a setembro de 2007. A dobutamina foi administrada em quatro estágios (10, 20, 30 e 40 µcg.kg-1.min-1) para pesquisa de isquemia miocárdica e iniciada com 5 µcg.kg- ¹.min-1 apenas na análise de viabilidade miocárdica. A atropina foi iniciada conforme os protocolos vigentes. Foram verificados dados clínicos, hemodinâmicos e efeitos adversos associados ao ecocardiograma sob estresse com dobutamina. Resultados: Durante os ecocardiogramas sob estresse com dobutamina, ocorreu angina típica (8,9%), pico hipertensivo (1,7%), ectopias ventriculares isoladas (31%), taquiarritmia supraventricular (1,89%), fibrilação atrial (0,76%) e taquicardia ventricular não sustentada (0,6%). Os efeitos adversos citados foram mais frequentes nos pacientes com ecocardiogramas sob estresse com dobutamina positivos para isquemia. A desaceleração sinusal paradoxal (0,16%) não ocorreu em ecocardiogramas sob estresse com dobutamina positivo. As três complicações graves ocorreram em ecocardiogramas sob estresse com dobutamina positivos para isquemia. Foram dois casos (0,02%) com fibrilação ventricular e um caso de síndrome coronariana aguda (0,01%). Não houve caso de taquicardia ventricular sustentada, ruptura cardíaca, assistolia ou óbito. Comparados aos exames concluídos, nos inconclusivos, os pacientes usaram menos atropina (81,5% versus 49,9%; p< 0,001) e mais betabloqueador (4,7% versus 19%; p< 0,001), apresentando mais pico hipertensivo (1,1% versus 14,2%; p = 0,0001) e taquicardia ventricular não sustentada (0,5% versus 2,2%; p< 0,001). Conclusão: O ecocardiograma sob estresse com dobutamina realizado de forma apropriada é seguro e apresenta elevada exequibilidade.

Background: Adverse effects and inconclusive results may occur on dobutamine stress echocardiography. Objective: To assess the safety and feasibility of dobutamine stress echocardiography in a large general population. Methods: A total of 10,006 dobutamine stress echocardiographies were performed between July 1996 and September 2007. Dobutamine was administered in four stages (10, 20, 30, and 40 µcg·kg-1·min-1) to research myocardial ischemia starting with 5 µcg·kg- ¹·min-1 to analyze myocardial viability. Atropine administration was initiated according to current protocols. Clinical, hemodynamic, and adverse effect data associated with dobutamine stress echocardiography findings were verified. Results: Typical angina (8.9%), hypertensive peak (1.7%), isolated ventricular ectopias (31%), supraventricular tachyarrhythmia (1.89%), atrial

Combined dipyridamole-exercise stress echocardiography for detection of myocardial ischemia in hemodialysis patients: an alternative to stress nuclear imaging.

BACKGROUND: Stress nuclear imaging is the noninvasive technique currently used to detect coronary artery disease (CAD) in dialysis patients. Stress echocardiography is recognized as an alternative to stress nuclear imaging for the general population. The aim of this study is to assess the diagnostic accuracy of stress echocardiography for detecting myocardial ischemia in hemodialysis patients. METHODS: Stress echocardiography and stress technetium-99m-tetrofosmin (Myoview; Amersham International Plc) imaging were performed simultaneously for 66 asymptomatic hemodialysis patients in a single session, using a combination of high-dose dipyridamole and symptom-limited exercise. Coronary angiography was performed in 44 patients with at least one abnormal noninvasive test result or who were considered high-risk despite normal noninvasive test results. RESULTS: Results for stress echocardiography were abnormal in 15 patients (22%); stress Myoview, in 14 patients (21%); and coronary angiography, in 12 patients (18%). The sensitivity of stress echocardiography for detecting myocardial ischemia (defined as stress Myoview defect) was 86%; specificity, 94%; positive predictive value, 80%; negative predictive value, 96%; and overall accuracy, 92%. The sensitivity of stress echocardiography for detecting CAD (defined as abnormal coronary angiography result) was 83%; specificity, 84%; positive predictive value, 67%; negative predictive value, 93%; and overall accuracy, 84%. Stress echocardiography and stress Myoview did not differ significantly in overall accuracy for detecting CAD (84% versus 91%; P = not significant). CONCLUSION: In hemodialysis patients, combined dipyridamole-exercise echocardiography is an accurate method to detect both myocardial ischemia and CAD and represents an alternative to stress nuclear imaging.

Dobutamine pharmacodynamics during dobutamine stress echocardiography and the impact of beta-blocker withdrawal: a report from the Women's Ischemic Syndrome Evaluation Study.

STUDY OBJECTIVES: To determine the pharmacodynamic parameters of dobutamine during dobutamine stress echocardiography (DSE) and to determine how beta-blocker withdrawal the evening before DSE affects responses to dobutamine during DSE. DESIGN: Retrospective analysis. SETTING: University medical center. PATIENTS: One hundred thirty-six women who had chest pain or other symptoms suggestive of myocardial ischemia and were considered to have a clinical indication for coronary angiography MEASUREMENTS AND MAIN RESULTS: Patients underwent DSE with dobutamine dosages titrated from 5 to 40 microg/kg/minute. The infusion was terminated if the patient reached target heart rate or symptoms developed. Those taking beta-blockers withheld their doses the evening before DSE. Traditional pharmacodynamic modeling revealed a wide range in responses to dobutamine. Data for 62% of patients not taking beta-blockers were described by the Emax (maximum heart rate response to dobutamine) model, whereas data for only 39% of patients taking beta-blockers were best described by this model (p = 0.01). Patients taking beta-blockers also had a smaller mean increment in left ventricular ejection fraction (10.8% +/- 4.2% vs 14.1% +/- 9.3%, p < 0.01), a trend toward a higher ED50 (dobutamine dosage rate causing half the maximum heart-rate response; median 16.8 microg/kg/min, p = 0.12) and a lower sigmoidicity factor determining the shape of the curve (median 2.1, p = 0.03). CONCLUSION: The response to dobutamine exhibits wide interpatient variability, even in the absence of beta-blockade. Nonetheless, in the absence of beta-blockers, in most patients the dobutamine response reaches a plateau by the time the maximum infusion rate (40 microg/kg/min) is reached. Withdrawal of beta-blockers the evening before DSE may be inadequate time for elimination of beta-blocker effect, requiring the addition of atropine to achieve the desired response during DSE.

Beta-blocker therapy for dynamic left-ventricular outflow tract obstruction.

BACKGROUND: In a small but significant group of elderly patients who present with breathlessness, dynamic left-ventricular outflow tract obstruction (DLVOTO) may be responsible for symptom generation. The aim of our study was to investigate the effect of beta-blockade on ventricular physiology and symptoms in patients with DLVOTO. METHODS: We performed a pilot study in 15 patients (age 76+/-10 years, mean+/-S.D., 14 female) with symptoms of exercise intolerance (New York Heart Association, NYHA, class 2.7+/-0.5). All patients had normal resting left ventricular (LV) systolic function together with DLVOTO based on the presence of basal septal hypertrophy and the development of high outflow tract velocities on stress echocardiography. All were commenced on oral atenolol (mean dose 45+/-19 mg), but this could not be tolerated in four patients due to a deterioration in clinical status. RESULTS: In the remaining 11 patients who could tolerate atenolol therapy, the rate pressure product was significantly lower (23%, P=0.028) and there was a marked reduction in LV outflow tract velocity (23%, P=0.001) following beta-blockade. Patient symptoms improved significantly following atenolol therapy, with a reduction in mean NYHA class from 2.8+/-0.4 to 1.5+/-0.5 (P<0.0001). CONCLUSIONS: Beta-blockade may represent a beneficial therapeutic approach in selected patients with DLVOTO as identified by stress echocardiography.

ß Blockers for prevention of exercise-induced left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy.

Whether treatment with ß blockers (BBs) is of benefit to patients with hypertrophic cardiomyopathy (HC) and provocable outflow obstruction (with none or with only mild heart failure symptoms) is largely unresolved. Thus, we prospectively studied 27 patients with HC (age 36 ± 15 years; 81% men) with New York Heart Association class I or II, without obstruction at rest, but with exercise-induced left ventricular outflow tract (LVOT) gradient of ≥ 30 mm Hg. Patients underwent exercise echocardiography at baseline and after treatment with nadolol (n = 18; 40 to 80 mg/day) or bisoprolol (n = 9; 5 to 10 mg/day), according to a prespecified protocol. Without the BBs, the postexercise LVOT gradient was 87 ± 29 mm Hg and >50 mm Hg in 25 patients (93%). After a 12 ± 4-month period of BB treatment, the postexercise LVOT gradient had decreased to 36 ± 22 mm Hg (p <0.001) and was virtually abolished (to 0 or <30 mm Hg) in 14 patients (52%), substantially blunted (≥ 20 mm Hg reduction) in 9 (33%), and unchanged in only 4 (15%). Severe postexercise obstruction (range 58 to 80 mm Hg) persisted in 6 patients (22% compared to 93% without BBs; p <0.001). Nonresponders (residual postexercise gradient of ≥ 30 mm Hg with BBs) were characterized by an increased body mass index (hazard ratio 2.03/1 kg/m(2), 95% confidence interval 1.2 to 3.4; p <0.05). In conclusion, in patients with HC with mild or no symptoms, treatment with BBs can prevent the development of LVOT obstruction triggered by physiologic exercise. These findings provide a rationale for the novel strategy of early prophylactic pharmacologic treatment with standard, well-tolerated doses of BBs in physically active patients with provocable gradients, aimed at effective prevention of the hemodynamic burden associated with dynamic obstruction.

Head to head comparison of transesophageal and transthoracic contrast-enhanced echocardiography during dobutamine administration for the detection of coronary artery disease.

Dobutamine stress echocardiography (DSE) has been shown to be a very useful non-invasive technique for the detection of coronary artery disease. However, inadequate transthoracic images preclude the use of DSE in a significant proportion of patients. Transesophageal (TEE) or transthoracic contrast echocardiography (CE) can however overcome this limitation. The comparison between the two techniques has never been investigated during a stress test. Therefore, we designed a prospective study to compare DSE-CE and DSE-TEE for the detection of coronary artery disease in patients with poor echo image quality. We studied 42 patients scheduled for quantitative coronary angiography. Prospective DSE-CE and DSE-TEE with maximum one day interval were performed in a random order. Significant coronary artery disease was detected in 30 patients, nine with single vessel disease and 21 with multivessel disease. Sensitivity of DSE was higher with CE than with TEE (90% vs 87%, p=NS). There was no significant difference with respect to specificity in both groups (100% vs 92%, p=NS). The diagnostic accuracy was similar in both groups (93% vs 88%, NS). The kappa value for identical interpretation of a stress echocardiography study was nearly identical with both modalities 0.75 to 0.78. In poorly echogenic patients, DSE-CE is a valuable alternative for the detection of myocardial ischemia in comparison with DSE-TEE. Because DSE-CE is more comfortable than TEE, it should be used in patients with suboptimal transthoracic echocardiograms for the evaluation of coronary artery disease during DSE.