Sahar S. Abdelmoneim

American Society of Echocardiography Consensus Statement on the Clinical Applications of Ultrasonic Contrast Agents in Echocardiography

UNLABELLED ACCREDITATION STATEMENT: The American Society of Echocardiography (ASE) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASE designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit.trade mark Physicians should only claim credit commensurate with the extent of their participation in the activity. The American Registry of Diagnostic Medical Sonographers and Cardiovascular Credentialing International recognize the ASEs certificates and have agreed to honor the credit hours toward their registry requirements for sonographers. The ASE is committed to resolving all conflict-of-interest issues, and its mandate is to retain only those speakers with financial interests that can be reconciled with the goals and educational integrity of the educational program. Disclosure of faculty and commercial support sponsor relationships, if any, have been indicated. TARGET AUDIENCE This activity is designed for all cardiovascular physicians, cardiac sonographers, and nurses with a primary interest and knowledge base in the field of echocardiography; in addition, residents, researchers, clinicians, sonographers, and other medical professionals having a specific interest in contrast echocardiography may be included. OBJECTIVES Upon completing this activity, participants will be able to: 1. Demonstrate an increased knowledge of the applications for contrast echocardiography and their impact on cardiac diagnosis. 2. Differentiate the available ultrasound contrast agents and ultrasound equipment imaging features to optimize their use. 3. Recognize the indications, benefits, and safety of ultrasound contrast agents, acknowledging the recent labeling changes by the US Food and Drug Administration (FDA) regarding contrast agent use and safety information. 4. Identify specific patient populations that represent potential candidates for the use of contrast agents, to enable cost-effective clinical diagnosis. 5. Incorporate effective teamwork strategies for the implementation of contrast agents in the echocardiography laboratory and establish guidelines for contrast use. 6. Use contrast enhancement for endocardial border delineation and left ventricular opacification in rest and stress echocardiography and unique patient care environments in which echocardiographic image acquisition is frequently challenging, including intensive care units (ICUs) and emergency departments. 7. Effectively use contrast echocardiography for the diagnosis of intracardiac and extracardiac abnormalities, including the identification of complications of acute myocardial infarction. 8. Assess the common pitfalls in contrast imaging and use stepwise, guideline-based contrast equipment setup and contrast agent administration techniques to optimize image acquisition.

Guidelines for the Cardiac Sonographer in the Performance of Contrast Echocardiography: A Focused Update from the American Society of Echocardiography

Thomas R. Porter, MD, FASE (Chair), Sahar Abdelmoneim, MD, J. Todd Belcik, BS, RCS, RDCS, FASE, Marti L. McCulloch,MBA, RDCS, FASE, Sharon L.Mulvagh,MD, FASE, Joan J. Olson, BS, RDCS, RVT, FASE, Charlene Porcelli, BS, RDCS, RDMS, FASE, Jeane M. Tsutsui, MD, and Kevin Wei, MD, FASE, Omaha, Nebraska; Rochester, Minnesota; Portland, Oregon; Houston, Texas; Charleston, South Carolina; S~ ao Paulo, Brazil

Safety of Contrast Agent Use During Stress Echocardiography: A 4-Year Experience From a Single-Center Cohort Study of 26,774 Patients

OBJECTIVES We evaluated the short- and long-term safety of contrast agents during stress echocardiography (SE). BACKGROUND Concerns about contrast agent safety led to revised recommendations for product use in the U.S. METHODS We studied 26,774 patients who underwent SE between November 1, 2003, and December 31, 2007. The 10,792 patients who comprised the contrast cohort received second-generation perfluorocarbon-based agents for left ventricular opacification during SE. The noncontrast cohort comprised 15,982 patients who had their first SE in the same period but without contrast agents. Short-term (< or = 72 h and < or = 30 days) and long-term (up to 4.5 years) end points were death and myocardial infarction (MI). Cox regression models were used. Immediate contrast agent-related adverse effects were also reported. RESULTS The contrast cohort had older patients (mean [SD] age, 65.8 [12.1] years vs. 62.6 [14.1] years; p < 0.001), a higher percentage of males (57.4% vs. 52.8%, p < 0.001), and higher-risk patients compared with the noncontrast cohort. In addition, dobutamine SE patients had greater cardiac risk than exercise SE patients. Abnormal SE findings in patients who received contrast agents were more frequent (32.4% vs. 27.9%, p < 0.001). The 2 cohorts had no statistical difference in the incidence of short-term events (death and MI). Within 72 h, 1 patient in the contrast cohort and 2 patients in the noncontrast cohort died (p = 0.54); 3 in the contrast cohort and 7 in the noncontrast cohort had MI (p = 0.92). Within 30 days, 37 patients (0.34%) in the contrast cohort and 57 patients (0.36%) in the noncontrast cohort died (p = 0.85); 17 patients (0.16%) in the contrast cohort and 16 patients (0.10%) in the noncontrast cohort had MI (p = 0.19). Adjusted hazard ratios were not different between cohorts for death (0.99; 95% confidence interval: 0.88 to 1.11) or MI (0.99; 95% confidence interval: 0.80 to 1.22). CONCLUSIONS The use of contrast agents during SE was not associated with an increased short-term or long-term risk of death or MI.

Microvascular Function in Takotsubo Cardiomyopathy With Contrast Echocardiography: Prospective Evaluation and Review of Literature

BACKGROUND Takotsubo cardiomyopathy (TC) mimics ST-elevation myocardial infarction without substantial angiographic stenosis. Coronary microvascular dysfunction has been proposed as a possible mechanism in TC. The aim of this study was to evaluate microvascular function in TC using real-time myocardial contrast echocardiography (MCE). METHODS Real-time MCE was performed within 24 hours of coronary angiographic diagnosis of TC. Myocardial perfusion was evaluated through qualitative and quantitative myocardial contrast echocardiographic analyses comparing normal segments with segments with dysfunctional wall motion (WM). RESULTS From January 2007 to January 2008, 11 patients received diagnoses of TC. Of these patients, 9 were prospectively enrolled (mean age, 70.9 +/- 17.5 years; 8 women). Qualitative and quantitative myocardial contrast echocardiographic analyses were feasible in 87% and 81% of segments. Overall, concordance between qualitative MCE and WM for normal versus abnormal analysis was observed in 71% of segments (kappa = 0.442, SE = 0.08). Significantly lower myocardial blood flow velocity (beta) and lower myocardial blood flow (Abeta) were detected in segments with dysfunctional WM compared with those with normal WM (beta = 0.55 +/- 0.39 vs 0.90 +/- 0.77, P = .009; Abeta = 5.31 +/- 3.92 vs 12.38 +/- 13.47, P = .002). In the discordant segments between qualitative MCE and WM, the quantitative perfusion parameters beta and Abeta were significantly lower in segments with dysfunctional WM compared with those with normal WM (beta = 0.22 +/- 0.20 vs 1.79 +/- 0.57, P = .01; Abeta = 1.90 +/- 1.1 vs 24.29 +/- 19.9, P = .02). Recovery of WM abnormalities was detected in all patients during follow-up echocardiography (mean, 60.3 +/- 66.0 days). No contrast-related side effects were reported. During mean follow-up of 5.9 +/- 4.6 months, there were no cardiac events, but 1 noncardiac death (from lung cancer) occurred. CONCLUSION TC is associated with abnormal myocardial perfusion detected with qualitative and quantitative MCE, indicative of microvascular dysfunction.

Regression of Paravalvular Aortic Regurgitation and Remodeling of Self-Expanding Transcatheter Aortic Valve: An Observation From the CoreValve U.S. Pivotal Trial

OBJECTIVES The aim of this study was to describe the natural history and clinical importance of paravalvular aortic regurgitation (PVAR) after CoreValve transcatheter aortic valve replacement (TAVR) and to relate these findings to the structural and hemodynamic changes documented by serial echocardiographic analysis. BACKGROUND PVAR after TAVR with the self-expanding CoreValve bioprosthesis has been shown to regress over time, but the time course and the mechanism of PVAR regression has not been completely characterized. METHODS Patients with severe aortic stenosis who underwent CoreValve TAVR and followed up to 1 year in the multicenter CoreValve U.S. Pivotal Trial (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement) were studied. Serial echocardiography studies were analyzed by an echocardiographic core laboratory. Annular sizing ratio was calculated from computed tomography measurements. Paired, as well as total, data were compared. RESULTS The CoreValve was implanted in 634 patients with a mean age of 82.7 ± 8.4 years. After a marked improvement noted at discharge, aortic valve velocity, mean gradient, and effective orifice area further improved significantly at 1 month (2.08 ± 0.45 m/s vs. 1.99 ± 0.46 m/s, p < 0.0001, 9.7 ± 4.4 mm Hg vs. 8.9 ± 4.6 mm Hg, p < 0.0001, and 1.78 ± 0.51 cm(2) vs. 1.85 ± 0.58 cm(2), p = 0.03, respectively). The improvement was sustained through 1 year. PVAR was moderate or severe in 9.9%, and of 36 patients with moderate PVAR at discharge and paired data, 30 (83%) improved at least 1 grade of regurgitation at 1 year. Annular sizing ratio was significantly associated with the degree of PVAR. CONCLUSIONS There was further improvement in aortic prosthetic valve hemodynamics and regression of PVAR up to 1 year compared with discharge after TAVR with CoreValve. These changes are possibly due to remodeling and outward expansion of the self-expandable CoreValve with nitinol frame. (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement [Medtronic CoreValve U.S. Pivotal Trial]; NCT01240902).

Safety of Contrast Agent Use during Stress Echocardiography in Patients with Elevated Right Ventricular Systolic Pressure: A Cohort Study

Background—Microbubble safety concerns led to changes in product recommendations for patients with pulmonary hypertension. Noninvasive estimation of right ventricular systolic pressure (RVSP) is equivalent to pulmonary artery systolic pressure in the absence of pulmonary outflow obstruction. We analyzed the short- and long-term outcomes of patients who received microbubble contrast and those who did not during stress echocardiography (SE) according to resting RVSP. Methods and Results—From November 2003 to December 2007, 26 774 patients underwent SE. RVSP (mean, 32.6±9.6 mm Hg) was measured in 16 434 patients. Of these, 6164 (37.5%) received contrast for left ventricular opacification and 10 270 (62.5%) did not. Short-term (≤72 hours and ≤30 days) and long-term (4.3 years) end points were death and myocardial infarction. Analysis was done for rest RVSP cut-points ≥35, ≥50, and ≥60 mm Hg and tricuspid regurgitant velocities ≥2.7 ms−1 and ≥3.5 ms−1. Adjusted Cox regression models were used. The contrast cohort comprised older patients (age, 67±12 versus 64±14 years; P<0.001), who were more likely to have positive SE results (35% versus 30%, P<0.001) compared with the noncontrast cohort. Using RVSP ≥50 mm Hg, there was no significant difference in short-term events between the contrast and noncontrast cohorts. For long-term events, there was no significant difference between both cohorts (adjusted hazard ratios [95% confidence intervals] for death, 1.10 [0.80 to 1.50], P=0.56; and myocardial infarction, 0.34 [0.11 to 1.03], P=0.06). Similar results were obtained at different RVSP and tricuspid regurgitant cut-points. Contrast agent-related adverse effects occurred in <1% of patients. Conclusion—RVSP had no impact on predisposition to adverse outcomes in patients undergoing contrast SE in the population studied.

Myocardial contrast echocardiography in biopsy-proven primary cardiac amyloidosis

Cardiac vasculature is affected in 88-90% of patients with primary cardiac amyloidosis (CA). Myocardial contrast echocardiography (MCE) relies on the ultrasound detection of microbubble contrast agents that are solely confined to the intravascular space, and are therefore useful in the evaluation of flow in the microvasculature. This is the first case report describing the use of MCE during vasodilator stress to evaluate coronary flow reserve in a patient with biopsy-proven primary CA and angiographically normal coronaries. Qualitative MCE demonstrated delayed replenishment of microbubbles during peak stress; quantitative analysis was consistent with a reduction in total myocardial blood flow and reserve values. Comparative imaging modalities including strain and strain rate imaging, magnetic resonance imaging, and myocardial scintigraphy were suggestive to the diagnosis of CA. In conclusion, MCE is a method for recognition of microvascular dysfunction, and might be considered as a useful tool to augment echocardiographic assessment in the early diagnosis of CA.

Quantitative myocardial contrast echocardiography during pharmacological stress for diagnosis of coronary artery disease: a systematic review and meta-analysis of diagnostic accuracy studies.

AIMS We conducted a meta-analysis to evaluate the accuracy of quantitative stress myocardial contrast echocardiography (MCE) in coronary artery disease (CAD). METHODS AND RESULTS Database search was performed through January 2008. We included studies evaluating accuracy of quantitative stress MCE for detection of CAD compared with coronary angiography or single-photon emission computed tomography (SPECT) and measuring reserve parameters of A, beta, and Abeta. Data from studies were verified and supplemented by the authors of each study. Using random effects meta-analysis, we estimated weighted mean difference (WMD), likelihood ratios (LRs), diagnostic odds ratios (DORs), and summary area under curve (AUC), all with 95% confidence interval (CI). Of 1443 studies, 13 including 627 patients (age range, 38-75 years) and comparing MCE with angiography (n = 10), SPECT (n = 1), or both (n = 2) were eligible. WMD (95% CI) were significantly less in CAD group than no-CAD group: 0.12 (0.06-0.18) (P < 0.001), 1.38 (1.28-1.52) (P < 0.001), and 1.47 (1.18-1.76) (P < 0.001) for A, beta, and Abeta reserves, respectively. Pooled LRs for positive test were 1.33 (1.13-1.57), 3.76 (2.43-5.80), and 3.64 (2.87-4.78) and LRs for negative test were 0.68 (0.55-0.83), 0.30 (0.24-0.38), and 0.27 (0.22-0.34) for A, beta, and Abeta reserves, respectively. Pooled DORs were 2.09 (1.42-3.07), 15.11 (7.90-28.91), and 14.73 (9.61-22.57) and AUCs were 0.637 (0.594-0.677), 0.851 (0.828-0.872), and 0.859 (0.842-0.750) for A, beta, and Abeta reserves, respectively. CONCLUSION Evidence supports the use of quantitative MCE as a non-invasive test for detection of CAD. Standardizing MCE quantification analysis and adherence to reporting standards for diagnostic tests could enhance the quality of evidence in this field.

Rapid Detection of Coronary Artery Stenoses With Real-Time Perfusion Echocardiography During Regadenoson Stress

Background— Real-time myocardial contrast echocardiography permits the detection of myocardial perfusion abnormalities during stress echocardiography, which may improve the accuracy of the test in detecting coronary artery stenoses. We hypothesized that this technique could be used after a bolus injection of the selective A2A receptor agonist regadenoson to rapidly and safely detect coronary artery stenoses. Methods and Results— In 100 patients referred for quantitative coronary angiography, real-time myocardial contrast echocardiography was performed during a continuous intravenous infusion of 3% Definity at baseline and at 2-minute intervals for up to 6 minutes after a regadenoson bolus injection (400 &mgr;g). Myocardial perfusion was assessed by examination of myocardial contrast replenishment after brief high mechanical index impulses. A perfusion defect was defined as a delay (>2 seconds) in myocardial contrast replenishment in 2 contiguous segments. Wall motion was also analyzed. The overall sensitivity/specificity/accuracy for myocardial perfusion analysis in detecting a >50% diameter stenosis was 80%/74%/78%, whereas for wall motion analysis it was 60%/72%/66% (P<0.001 for differences in sensitivity). Sensitivity for myocardial perfusion analysis was highest on images obtained during the first 2 minutes after regadenoson bolus (P<0.001 compared with wall motion), whereas wall motion sensitivity was highest at the 4-to-6–minute period after the bolus. No significant side effects occurred after regadenoson bolus injection. Conclusions— Regadenoson real-time myocardial contrast echocardiography appears to be a feasible, safe, and rapid noninvasive method for the detection of significant coronary artery stenoses. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT0087369.

Assessment of Myocardial Perfusion during Adenosine Stress Using Real Time Three‐Dimensional and Two‐Dimensional Myocardial Contrast Echocardiography: Comparison with Single‐Photon Emission Computed Tomography

Objectives: To evaluate diagnostic accuracy of adenosine two‐dimensional and three‐dimensional myocardial contrast echocardiography (2D‐ and 3D‐MCE) compared with single‐photon emission computed tomography (SPECT) for assessing myocardial perfusion. Methods: From January through August 2007, patients with known or suspected CAD who were referred for SPECT underwent simultaneous adenosine 2D‐MCE and 3D‐MCE (live and full volume [FV]). Perfusion and wall motion in 17 segments in the left anterior descending, left circumflex, and right coronary artery territories were analyzed. Results: We studied 30 patients: mean (SD) age, 72.6 (8.2) years; 19 (63%) men. Perfusion by SPECT was abnormal in 13 patients (43%). When comparing MCE with SPECT, sensitivity was comparable for 2D‐MCE, 92%; live 3D‐MCE, 91%; and FV 3D‐MCE, 90%. Specificity was comparable for 2D‐MCE, 75%; live 3D‐MCE, 69%; and FV 3D‐MCE, 79%. Agreement between live 3D‐MCE and 2D‐MCE was 92% (κ[SE], 0.83 [0.17]) and between FV 3D‐MCE and 2D‐MCE, 88% (κ[SE], 0.76 [0.13]). For eight patients in whom SPECT showed reversible defects, live 3D‐MCE correctly identified defects in seven (88%), whereas FV 3D‐MCE correctly identified them in five (63%) (P = 0.57). Conclusion: Myocardial perfusion assessment is feasible by 3D‐MCE with the advantage of rapid, facile acquisition and offline image manipulation. (Echocardiography 2010;27:421‐429)